Effects of risperidone on dopamine receptor subtypes in developing rat brain.

The atypical antipsychotic risperidone is often prescribed to pediatric patients with neuropsychiatric disorders, though its effects on the developing brain remain unclear. Accordingly, we studied the effects of repeated treatment of risperidone on dopamine receptors in brain regions of juvenile rat. Levels of dopamine receptors (D(1), D(2), D(3), D(4)) in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0 mg/kg/day) increased levels of D(1) receptors in nucleus accumbens and caudate-putamen of juvenile, but not adult rats. Conversely, all three doses of risperidone dose-dependently increased D(2) labeling in medial prefrontal cortex and hippocampus, and D(4) receptor in nucleus accumbens, caudate-putamen and hippocampus of juvenile animals as well as in adults. Only the high dose of risperidone (3.0 mg/kg) increased D(2) receptors in caudate-putamen in both juvenile and adult brain. D(3) receptors were not altered by risperidone in any brain region at any dose or age. The findings indicate dose-dependent effects of risperidone on dopamine receptors in developing animals, and that juvenile animals are more sensitive than adults to the cerebral effects of risperidone.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Traumatic cervical Brown-Sequard and Brown-Sequard-plus syndromes: the spectrum of presentations and outcomes.

Brown-Sequard syndrome (BSS) and Brown-Sequard-plus syndrome (BSPS) are characterised by asymmetrical paresis with hypalgesia more marked on the less paretic side. This study examined the clinical features of 38 patients (30 males and 8 females; mean age = 32 years) with traumatic cervical BSS or BSPS who underwent comprehensive inpatient rehabilitation. Twenty two injuries were caused by road traffic accidents, 8 by penetrating injuries, 5 by diving injuries, and 3 by other causes. After an average of 35 days in acute care and 79 days in rehabilitation, 37 patients had increased muscle strength, all 38 patients improved functional abilities, 29 patients walked independently, 34 had spontaneous bladder emptying, 36 were discharged home, and 14 were employed. Statistically significant increases (p less than 0.001) were made in modified Barthel index functional scores between admission and discharge. Patients with BSPS had a better prognosis than did those with 'pure' BSS. Patients with predominant upper limb weakness had more favourable outcomes than did those with predominant lower limb weakness. Few other potentially predictive demographic, injury, or neurological factors were associated with functional outcome. Patients with BSS or BSPS generally have a good prognosis for neurological and functional improvement.     

Intraocular pressure and axial length in children

The intraocular pressure and the anteroposterior length of the eye are of great clinical importance for the diagnosis and management, before and after surgery, of congenital glaucoma. It is well-known that normal intraocular pressure in children is different from the normal levels in adults. We performed measurements of intraocular pressure and axial length in 141 children who had been admitted for eye problems other than glaucoma. The intraocular pressures were measured with the Perkins hand-held applanation tonometer at the beginning of general anesthesia. Simultaneously, A-scan ultra-sound measurements of the axial lengths of the eyes were made. In 10 children under the age of two years, the intraocular pressure was 11.85 +/- 1.35 mmHg. In 79 children from two to seven years, the intraocular pressure was 12.80 +/- 1.73 mmHg. In 52 children from seven to 15 years, the intraocular pressure was 13.31 +/- 1.79 mmHg. The axial lengths of the eyes in children under the age of two years, from two to seven years, and from seven to 15 years, were 21.31 +/- 0.97 mm, 22.04 +/- 0.92 mm, and 23.22 +/- 1.00 mm, respectively. These results were considered to be guidelines for measuring intraocular pressure and axial length in children suspected of having congenital glaucoma. The differences of intraocular pressures stated by other authors are due to early measurement of the intraocular pressure at the beginning of general anesthesia.     

Structural Characterization of Variant Forms of Arylsulfatase A that Associate with Alcoholism

Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type III_a and normal type IV_a, have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type III_a compared with nonalcoholic psychiatric and normal controls. Individuals with the III_a enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the III_a and IV_a individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from III_a individuals lacks an N -linked glycan found in ASA from IV_a individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N -linked carbohydrate or phosphorylation exist between the fibroblast ASA from III_a and IV_a individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types.     

Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?

The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha-hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation.     

Outcome after traumatic frontal intracerebral haemorrhage: a comparison of unilateral and bilateral haematomas

Frontal intracerebral haemorrhage (ICH) is a common result of cranial trauma. Outcome differences between bilateral and unilateral frontal ICH are not well studied but would be valuable to predict prognosis in clinical practice. Two aims are proposed in this study: first to compare the risk of developing delayed ICH after bilateral or unilateral frontal ICH, and second to determine the variables helpful to predict outcome according to the Glasgow Outcome Scale (GOS). Between January 1993 and December 1997, 694 consecutive patients with traumatic ICH were admitted to the Chang Gung Medical Center within 24 h of the trauma. Patients with ICH in sites other than the frontal lobes were excluded. A total of 161 cases (mean age 46.3+/-20.3 years), including 57 bilateral (mean age 52.5+/-18.7 years) and 104 unilateral (mean age 42.9+/-20.5 years) traumatic frontal ICH were studied. Twenty-eight of 57 patients (49%) with bifrontal ICH versus 17 of 104 patients (16%) with unilateral frontal ICH had a further, delayed ICH. In 42 of 45 patients (93%) with delayed ICH, this occurred within 5 days of the initial trauma. Multivariate logistic regression was used to select significant predictors of outcome. We found that delayed ICH (p<0.001), age (p=0.004) and mechanism of injury (p=0.001) explained the worse outcome in patients with bifrontal ICH. The best-fitting logistic regression model included three variables: delayed ICH (p=0.011), initial GCS (p=0.023), and a sum score of clinical and radiological variables (p=0.003). Bifrontal ICH tended to occur in older patients after a fall and was associated with a higher risk of developing delayed ICH or brain stem compression compared to unilateral ICH damage. Using these three variables - delayed ICH, initial GCS, and the sum score - in a logistical regression model is useful to predict outcome in patients with traumatic frontal ICH and may aid patient management.     

Carotid intima-media thickness in Parkinson's disease.

There have been a few studies and inconsistent results regarding the coincidence of Parkinson's disease (PD) and atherosclerotic diseases, such as cerebrovascular disease. Carotid intima-media thickness (IMT) is a known marker for subclinical atherosclerosis. The aim of this study was to investigate the carotid IMT between PD patients and controls. We studied 43 patients with PD and 86 matched controls. The carotid IMT in PD patients was significantly smaller than in controls (0.796 +/- 0.179 mm vs. 0.913 +/- 0.237 mm, P < 0.05). In multivariate analysis, the carotid IMT was inversely associated with the duration of levodopa medication and the severity of PD. These results suggest that PD patients have a lower risk of atherosclerosis.