Altered cerebral energy utilization in late life depression.

BACKGROUND: Global and regional changes in cerebral energy utilization are reported to characterize late life depression. METHODS: Twenty seven subjects with late life depression (9 prior to starting medication, 18 after starting) and 27 matched controls were evaluated with cordance, a quantitative EEG measure that reflects cerebral energy utilization. RESULTS: Global and focal (anterior and centrotemporal) differences were present in theta-band cordance between unmedicated depressed and control subjects. Depressed subjects receiving treatment had cordance patterns similar to controls. CONCLUSIONS: The presence of both diffuse and focal disturbances in energy utilization prior to initiating treatment indicates that cordance detects altered cerebral physiology in depressed patients, and that this measure may also be sensitive to treatment interventions.

Concurrent validity of the Neurobehavioral Cognitive Status Exam subtests.

The Neurobehavioral Cognitive Status Exam (NCSE) is a screening measure that assesses numerous neuropsychological (NP) domains. Fifty-four patients completed the NCSE and common NP tests assessing similar abilities. Most subtest screens (brief items that determine whether additional testing should occur) exhibited low false negative rates, but high false positive rates, based upon performance on the follow-up metric items. Each subtest was significantly correlated with the associated NP test. However, using performance on the NP tests as the 'gold standard', the NCSE subtests classified impaired and unimpaired patients at a much lower than expected rate. The latter results draw into question the efficacy of the NCSE subtests in delineating domain-specific cognitive functioning.

Using the neurobehavioral cognitive status examination as a screening measure for older adults.

We evaluated the ability of the Neurobehavioral Cognitive Status Examination (NCSE) to accurately distinguish between healthy older adults and geriatric patients suffering from dementia. Although the NCSE correctly identified all dementia patients, it produced an unacceptably high rate of false positives among the healthy elderly (70%). Despite the NCSE's lack of specificity when using the recommended classification criteria, significant group differences were found on several individual subscales and on the total number of subscales passed. These findings suggest the need to further evaluate the appropriateness of the geriatric norms for the NCSE and highlight some of the unique considerations involved in the assessment of older adults.

Brain structure and function and the outcomes of treatment for depression.

BACKGROUND: Depressed patients have a variety of brain structural alterations, the most common being atrophy and deep white-matter lesions. Alterations in brain function also are common, particularly regional decreases in cerebral metabolism and perfusion. METHOD: We review here the evidence that alterations in brain structure and function may explain some of the heterogeneity in outcomes of depression. We also report initial results suggesting that measurement of brain structure and function may help to predict outcomes of treatment for depression. Brain structure was examined using three-dimensional reconstruction and volumetric analysis of magnetic resonance imaging (MRI) scans. Brain function was examined using quantitative electroencephalography (QEEG), performed at baseline and serially during the course of treatment. QEEG measures included coherence (a measure of synchronized activity between brain regions) and cordance (a measure strongly associated with regional cerebral perfusion). RESULTS: Depressed patients have been reported to have larger volumes of white-matter lesions than controls. We have found that some types of white-matter lesions are associated with lower coherence and that subjects with low coherence had significantly poorer outcomes of treatment for depression at 2-year follow-up. Depressed subjects had low cordance at baseline, which decreased further during the course of effective treatment. Subjects who did not improve had little or no change in cordance. Changes in cordance were detected prior to the onset of clinical response, with decreases seen as early as 48 hours after the initiation of treatment in subjects who showed eventual response. CONCLUSION: These preliminary results suggest that functional imaging using QEEG may be useful for assessing, and possibly predicting, outcomes of treatment for depression.

Relationships between EEG coherence and neuropsychological tests in dementia.

Previous research has demonstrated differences in resting state EEG coherence among groups of subjects with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal elderly controls. Since reduced coherence between brain sites has been thought to reflect functional disconnection between brain areas, we hypothesized that decreased coherence would be associated with cognitive dysfunction as assessed by neuropsychological tests. We correlated several neuropsychological tests with four coherence variables and found that reduced coherence was associated with impairment on specific neuropsychological tests in ways that conform to and supplement current knowledge about the localization of brain functions. The results are consistent with the hypothesis that coherence reflects a functional breakdown in communication between brain areas, and that coherence may be a more precise way to localize brain function than other EEG variables.

Idiopathic sudden sensorineural hearing loss in patients undergoing long-term haemodialysis.

Idiopathic sudden sensorineural hearing loss (ISHL) has been recently recognized and is increasing in frequency in patients undergoing long-term haemodialysis. Although this is one of the annoying complications impairing quality of life in haemodialysis patients, there has been little clinical evidence about ISHL in haemodialysis patients until now. We have examined retrospectively the clinical features of 6 ISHL patients, 3 males and 3 females, with a mean age of 54 years, who underwent regular haemodialysis with a mean haemodialysis duration of 90 months from 1985 to 1989. Although a specific cause for ISHL could not be identified in this study, more precise clinical features of ISHL in patients undergoing haemodialysis have been elucidated. ISHL seemed to develop more frequently in haemodialysis patients and occurred in patients undergoing haemodialysis for a relatively long time, being independent of the high-frequency-deficit type hearing disturbances usually observed in the early course of haemodialysis therapy. Above all, diabetic haemodialysis patients were more susceptible to ISHL, occurring in 4 cases out of 6. Its prognosis was not necessarily bad, showing a recovery rate of 83%, but more effective therapy should be explored for improving the quality of life in haemodialysis patients.

Case report: Wegener's granulomatosis accompanied by communicating hydrocephalus.

A case of Wegener's granulomatosis (WG) accompanied by communicating hydrocephalus is described. An elderly woman with rapidly progressive renal failure was referred to the authors' hospital. Renal histologic study showed necrotizing granulomatous glomerulonephritis with some multinucleated giant cells, which suggested a diagnosis of WG. After admission, a gait disturbance, incontinence, and dementia developed in the patient. Diagnostic procedures including lumbar puncture, computed tomography (CT), and scintigraphy showed findings compatible with communicating hydrocephalus with a normal cerebrospinal fluid (CSF) pressure. Removal of 20 mL of CSF led to a marked improvement in symptoms. Because the presence of subarachnoid hemorrhage, meningitis, and brain tumor was excluded, the final diagnosis was communicating hydrocephalus secondary to WG.

Thyrotoxicosis with low serum total T3 level in patients with destructive thyroiditis and non-thyroidal illness.

The serum total T3 level, evaluated in 687 patients with thyrotoxicosis diagnosed by an elevated serum free T4 level and suppressed serum TSH level, was found to be high in 98.1% and normal in 1.9% of 592 patients with Graves' hyperthyroidism, and high in 75.8%, normal in 21.1% and low in 3.2% of 95 patients with destructive thyroiditis. Non-thyroidal illness was found in about a third of the patients with thyrotoxicosis and a normal serum total T3 level. The serum total T3 level was low with elevated serum thyroglobulin and reverse T3 levels in three patients with severe non-thyroidal illness, in whom the thyroidal radioactive iodine uptake was suppressed and the thyrotoxicosis resolved spontaneously with a normalization of the serum total T3 level after recovery from the destructive thyroiditis and non-thyroidal illness. It is therefore concluded that thyrotoxicosis with a low serum total T3 level, partially due to associated non-thyroidal illness, is more frequently found in patients with destructive thyroiditis than in those with Graves' hyperthyroidism.

Confabulation in Alzheimer's disease.

Confabulation is present when memory is disturbed, but does it occur in Alzheimer's disease (AD) where memory abnormalities are often severe? In this study, confabulation was assessed prospectively in 26 AD patients and 15 normal elderly (NE) controls using a neuropsychological battery specifically designed to assess different types of memory errors. The results indicated that the AD group made significantly more verbal intrusions than the NE group. These findings provide evidence for the feasibility of eliciting confabulatory-type behavior during clinical assessment and support previous reports which have documented verbal intrusions as a common accompaniment of the memory impairment manifested by AD patients.

CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO.

To investigate the effects of anemia correction with recombinant human erythropoietin (rhEPO) on both cerebral blood flow and oxygen metabolism in hemodialysis (HD) patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and metabolic rate for oxygen (rCMRO2) were measured by positron emission tomography in five HD patients, and the data were compared with eight nondemented controls who had neither anemia nor uremia. In the HD patients, 1,500 U of rhEPO were administered intravenously three times a week to achieve a 10% increase in hematocrit (Hct) as an absolute value. Before rhEPO administration, the hemispheric rCMRO2 in HD patients was 1.48 +/- 0.09 (SE) ml.min-1.100 ml-1, which was significantly lower than that of 2.18 +/- 0.10 in the controls (P less than 0.01). In contrast, both rCBF and rOEF were significantly greater in the HD patients than the control, being 40 +/- 3 vs. 32 +/- 3 ml.min-1.100 ml-1 for rCBF (P less than 0.02) and 49 +/- 1 vs. 38 +/- 1% for rOEF (P less than 0.001). After treatment with rhEPO, Hct rose significantly from 21 +/- 1 to 31 +/- 1% in HD patients (P less than 0.001). There were significant reductions in both the hemispheric rCBF to 32 +/- 1 ml.min-1.100 ml-1 (P less than 0.01) and rOEF to 42 +/- 1% (P less than 0.01). However, the hemispheric rCMRO2 remained low at 1.58 +/- 0.06 ml.min-1.100 ml-1 even after rhEPO treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of calcium supplementation in patients with mild renal failure.

A low-protein diet has been shown to be effective in the prevention of progression of renal failure. However, the role of protein and that of phosphate intake have not been definitely separated. To determine the use of calcium (CaCO3) as a phosphate binder and a possible hypotensive agent, we performed a prospective, double-blind study of oral calcium in patients with mild-to-moderate renal failure (SCr less than 5.0 mg/dl). Thirty-six patients (20 m, 16 f) were studied. After a 2-month control period, either CaCO3 (6 g/day, 12 Cap) or placebo was given for 3 months. There was no significant difference in BUN, S-Sr, S-Ca, S-Pi, 24-hour Ccr, and blood pressure during the study period both in the genuine and the placebo group. Urine phosphate was decreased by about 50% in the CaCO3 group. Calcium carbonate is feasible as a phosphate binder for patients with mild-to-moderate renal failure.

Haemodynamic effect of recombinant human erythropoietin on hypotensive haemodialysis patients.

The haemodynamic effects of recombinant human erythropoietin (rHuEpo) on anaemic haemodialysis patients suffering from chronic hypotension were examined. rHuEpo increased the haematocrit to around 30% and increased diastolic blood pressure by 12.4%, statistically significant. Correspondingly, the total peripheral resistance index increased 42.3% while the cardiac index decreased 24.4% (P less than 0.05) respectively. Blood volume, plasma renin activity and plasma noradrenaline did not change significantly. The extent of blood pressure elevation and haemodynamic alteration did not differ from our previous report on anaemic haemodialysis patients without hypotension. The incidence of hypotensive episodes and fluid supplementation did not change significantly after rHuEpo treatment. In conclusion, by using rHuEpo, approximately a 10% increase of blood pressure can be expected. However no substantial improvement in hypotensive episodes can be expected in chronic haemodialysis patients suffering from hypotension.

Dose dependency of germanium-dioxide-induced nephrotoxicity in rats.

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.

Advantage of early initiation of aluminum hydroxide administration for the prevention of experimental progressive renal disease.

Aluminium hydroxide, a phosphate binder, is regarded as a strong candidate to halt the progression of chronic renal disease. In order to determine the most effective time to start treatment, aluminium hydroxide was administered either immediately (ADR-0w), or at 8 weeks (ADR-8w) or 16 weeks (ADR-16w) after repeated injection of Adriamycin (ADR) inducing glomerular sclerosis. In the aluminium hydroxide-untreated group the survival rate at the end of the experiment was 50%, while the early initiation of aluminium hydroxide (ADR-0w) resulted in a greater survival rate of 90%. Serum phosphate concentration and serum calcium-phosphate product were significantly less in the aluminium hydroxide groups (ADR-0w, 8w, 16w) than in the untreated group after week 20. Urinary protein excretion was significantly less in the ADR-0w and ADR-8w groups at week 12 or 16 compared to the aluminium hydroxide-untreated group. Blood urea nitrogen in the aluminium hydroxide groups was significantly less than that in the untreated group at week 34. Histological examination revealed that glomerular sclerosis was less severe in the ADR-0w and ADR-8w groups than in the aluminium hydroxide-untreated group, and glomerular hypertrophy was significantly decreased in the ADR-0w group. We conclude that early treatment with aluminium hydroxide was effective in preventing renal deterioration in focal glomerular sclerosis induced by Adriamycin.

Effect of different doses of aluminium hydroxide on renal deterioration and nutritional state in experimental chronic renal failure.

To investigate the effects of aluminium hydroxide (AH), a phosphate binder, on the progress of chronic renal diseases, high doses (9.6 g/kg/day, group ADR-H), moderate doses (2.4 g/kg/day, group ADR-M), and low doses (1.2 g/kg/day, group ADR-L) of the compound, were orally administered for 34 weeks to rats with Adriamycin (ADR)-induced focal glomerular sclerosis. Serum creatinine and blood urea nitrogen were significantly lower in either group ADR-H or ADR-M than in group ADR at week 34. Urinary protein excretion was significantly lower in group ADR-H than in group ADR in all observation periods and was also lower in group ADR-M than in group ADR at weeks 28 and 32. Both glomerular sclerosis and tubular change were significantly less severe in group ADR-H, while tubular change was less marked in group ADR-M than in group ADR. These results revealed that phosphate depletion was induced, and progressive renal failure was ameliorated in proportion to the dosing of AH. On the other hand, body weight was significantly smaller in group ADR-H than in group ADR in more than half of the observation period. In conclusion, a high dose of AH may adversely affect the nutritional state irrespective of having an extremely protective effect on progress of renal dysfunction. Appropriate doses of AH should be used to prevent the renal deterioration.

A case of cardiac injury and acute renal failure induced by electrical burn.

Reported is a case of electrical burn associated with cardiac injury and acute renal failure in a 21-year-old man. After coming into contact with a high-tension cable, he became drowsy and oliguria developed. Twenty-four hemodialyses were required. Although the ECG findings revealed an inferior wall myocardial infarction, neither cardiac scintigram (201TlCl) nor ultrasonic cardiography revealed any local lesions. In this case the cardiac damage following electrical burn appeared different from true myocardial infarction.

Subacute nephrotoxicity of germanium dioxide in the experimental animal.

Germanium (Ge; atomic number 32, atomic weight 72.6) belongs to IVb group of the Periodic Table and is found as a trace metal in soil, rocks, plants, and animals. It is widely used in industry because of its semiconductive nature. Some biological activities have been shown in Ge derivatives. Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2)-containing compounds have been reported in Japan. This study aimed to investigate subacute nephrotoxicity of GeO2 in Lewis male rats. The rats were treated orally with GeO2 for 13 weeks (GeO2 group) and were compared with those treated with GeO2 for only the first 4 weeks (GeO2-4-week group) and with untreated controls. Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance. Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group. However, daily urinary protein excretion or urinalysis did not differ among the groups. Kidney weight and Ge content of tissues were significantly elevated in the GeO2 group. With the light microscope, vacuoles and the depositions of PAS-stained particles, which correspond to electron-microscopic dense granules in the swollen mitochondria, were predominantly observed in distal tubular epithelium in the GeO2 group. Even in the GeO2-4-week group of rats, serum creatinine was increased and the above-mentioned histological abnormalities were observed, but were less intense.

Effect of swimming exercise on the progress of renal dysfunction in rat with focal glomerulosclerosis.

The effect of exercise on the progression of experimental renal disease was studied in adriamycin (ADR)-treated rats, a model of sclerosing glomerulonephritis with nephrotic syndrome. Two hours of daily swimming exercise was carried out for 20 weeks in ADR-treated male Lewis rats fed with either an ad libitum intake of regular chow (group 1) or a restricted amount of food (group 3), which was equal to the amount of food freely ingested by ADR-treated rats not undergoing swimming exercise (group 2). Group 3 resulted in a significantly lower serum creatinine, higher inulin clearance and lower glomerular sclerosis index compared to group 2. The progress of renal dysfunction did not differ significantly between group 1 and group 2. Hyperlipidemia, especially, hypertriglyceridemia was significantly lower in the exercise groups than in the sedentary group. Among all the rats, inulin clearance was inversely correlated with either cholesterol (r = 0.560, p less than 0.01) or triglyceride (r = 0.423, p less than 0.05) and the glomerular sclerosis index correlated positively with cholesterol (r = 0.599, p less than 0.005). Systolic blood pressure was 10 mm Hg lower in group 3 than in group 2 and the difference was significant. It is concluded that swimming exercise with a relative restriction of food intake can improve hyperlipidemia and prevent progressive renal dysfunction in ADR-induced nephritic rats.