Plasma glucose levels and outcome after aneurysmal subarachnoid hemorrhage

Plasma glucose levels were studied in 616 patients admitted within 72 hours after subarachnoid hemorrhage (SAH). Glucose levels measured at admission showed a statistically significant association with Glasgow Coma Scale scores, Botterell grade, deposition of blood on computerized tomography (CT) scans, and level of consciousness at admission. Elevated glucose levels at admission predicted poor outcome. A good recovery, as assessed by the Glasgow Outcome Scale at 3 months, occurred in 70.2% of patients with normal glucose levels (< or = 120 mg/dl) and in 53.7% of patients with hyperglycemia (> 120 mg/dl) (p = 0.002). The death rates for these two groups were 6.7% and 19.9%, respectively (p = 0.001). The association was still maintained after adjusting for age (> or < or = 50 years) and thickness of clot on CT scans (thin or thick) in the subset of patients who were alert/drowsy at admission. Increased mean glucose levels between Days 3 and 7 also predicted a worse outcome; good recovery was observed in 132 (73.7%) of 179 patients who had normal mean glucose levels (< or = 120 mg/dl) and 160 (49.7%) of 322 who had elevated mean glucose levels (> 120 mg/dl) (p < 0.0001). Death occurred in 6.7% and 20.8% of the two groups, respectively (p < 0.0001). It is concluded that admission plasma glucose levels can serve as an objective prognostic indicator after SAH. Elevated glucose levels during the 1st week after SAH also predict a poor outcome. However, a causal link between hyperglycemia and outcome after delayed cerebral ischemia, although suggested by experimental data, cannot be established on the basis of this study.     

Synthesis of deoxyglucose-1-phosphate, deoxyglucose-1,6-bisphosphate, and other metabolites of 2-deoxy-D-[14C]glucose in rat brain in vivo: influence of time and tissue glucose level

When the kinetics of interconversion of deoxy[14C]glucose ([14C]DG) and [14C]DG-6-phosphate ([14C]DG-6-P) in brain in vivo are estimated by direct chemical measurement of precursor and products in acid extracts of brain, the predicted rate of product formation exceeds the experimentally measured rate. This discrepancy is due, in part, to the fact that acid extraction regenerates [14C]DG from unidentified labeled metabolites in vitro. In the present study, we have attempted to identify the 14C-labeled compounds in ethanol extracts of brains of rats given [14C]DG. Six 14C-labeled metabolites, in addition to [14C]DG-6-P, were detected and separated. The major acid-labile derivatives, DG-1-phosphate (DG-1-P) and DG-1,6-bisphosphate (DG-1,6-P2), comprised approximately 5 and approximately 10-15%, respectively, of the total 14C in the brain 45 min after a pulse or square-wave infusion of [14C]DG, and their levels were influenced by tissue glucose concentration. Both of these acid-labile compounds could be synthesized from DG-6-P by phosphoglucomutase in vitro. DG-6-P, DG-1-P, DG-1,6-P2, and ethanol-insoluble compounds were rapidly labeled after a pulse of [14C]DG, whereas there was a 10-30-min lag before there was significant labeling of minor labeled derivatives. During the time when there was net loss of [14C]DG-6-P from the brain (i.e., between 60 and 180 min after the pulse), there was also further metabolism of [14C]DG-6-P into other ethanol-soluble and ethanol-insoluble 14C-labeled compounds. These results demonstrate that DG is more extensively metabolized in rat brain than commonly recognized and that hydrolysis of [14C]DG-1-P can explain the overestimation of the [14C]DG content and underestimation of the metabolite pools of acid extracts of brain. Further metabolism of DG does not interfere with the autoradiographic DG method.     

Tempora mutantur, nos et mutamur in illis!

In March 1992, KAP investigation and HIV blood test were carried out for 860 drug users and 82 spouses in Ruili, Luxi, Longchuan of Yunnan Province, China. The results show that there were 285 IDUs (33.1%) among 860 drug users. Among 282 blood samples of IDUs, the HIV infection rate was 49.0%, highest in Ruili (81.8%, 63/77), then Longchuan (44.6%, 77/166), lowest in Luxi County (5.1%, 2/36). Twelve new HIV+ were found from 75 persons, who had been tested as HIV- in recent two years. Sixty-two blood samples were collected among 82 spouses of IDUs with HIV+, 6 were HIV+ (9.8%), with an increase of 6.7% comparing with results of the investigation two-years ago (3.1%, 2/64).     

Ganglioside GM1 protects cAMP 3'5':phosphodiesterase from inactivation caused by lipid peroxidation in brain synaptosomes of rats

The preincubation of synaptosomes with nanomolar concentrations of ganglioside GM1 was shown to protect Ca(2+)-dependent and Ca(2+)-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca(2+)-dependent phosphodiesterase activity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the control activity if synaptosomes were preincubated with 10(-8)M GM1, the difference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosides were found to prevent to a great extent malonic dialdehyde (MDA) accumulation and to protect polyenoic fatty acids from oxidative destruction. The ability of gangliosides to protect phosphodiesterase from inactivation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct activation of the enzyme as well, 10(-7) M of ganglioside GM1 having the maximal activating effect. In contrast to alpha-tocopherol and other antioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems.     

Comparison of spontaneously released endothelium-derived relaxing factor in cerebral and extracerebral arteries in rabbits

To investigate regional differences in spontaneously released endothelium-derived relaxing factor (EDRF), a bioassay of spontaneously released EDRF was performed on rabbit basilar, ear, common carotid and thoracic arteries using an isometric tension measurement technique and a measurement of cyclic guanosine monophosphate (cGMP) content in the vascular smooth muscle. The amount of spontaneously released EDRF was higher in the basilar artery than in any other arteries examined (p < 0.01). The levels of cGMP were 57.3 +/- 4.4 (n = 7) in basilar, 26.5 +/- 4.3 (n = 6) in ear, 24.5 +/- 2.3 (n = 11) in common carotid, and 30.3 +/- 3.8 pmol/g tissue (n = 8) in thoracic artery with endothelium, while endothelium-denuded arteries showed 24.2 +/- 6.6 (n = 5), 17.5 +/- 5.1 (n = 6), 20.1 +/- 2.9 (n = 7) and 14.4 +/- 2.3 pmol/g tissue (n = 8) in the same order. Haemoglobin (10(-5) M, incubated with the artery for 5 min, significantly reduced the level of cGMP in all vessels with endothelium: 35.3 +/- 4.4 (basilar), 16.0 +/- 2.1 (ear), 14.0 +/- 1.9 (common carotid) and 8.7 +/- 1.2 pmol/g tissue (thoracic artery). Since endothelium-dependent relaxation is associated with a rise in the cGMP content of the smooth muscle cell, the data of cGMP measurement in addition to the bioassay of spontaneously released EDRF in tension measurement suggests that the spontaneous release of EDRF is much greater in the basilar artery than in extracerebral arteries. It is concluded that the intensity of the spontaneously released EDRF is relatively higher in the intracerebral artery than in the extracerebral artery.     

External carotid artery ligation for life-threatening hemorrhage in exsanguinating orbital facial congenital hemangiopericytoma

A 7-week-old infant with a locally invasive, orbital, congenital hemangiopericytoma underwent emergency external carotid artery (ECA) ligation for exsanguinating hemorrhage from an intraoral biopsy site. ECA ligation was successful in controlling the life-threatening hemorrhage and in reducing tumor size and vascularity. The location and extensive nature of the tumor prevented primary excision. Preoperative adjuvant chemotherapy was unsuccessful in controlling tumor growth. After ECA ligation, with reduction in tumor bulk and blood supply, the tumor was radically excised. This technique has important implications in the management of patients with extensive hemangiopericytomas or sino-facial tumors previously regarded as unresectable and which present with life-threatening hemorrhage.     

Corticostriatal mechanisms of behavior

This article presents the results of three series of experiments on cats, dogs, and lower primates, performed to investigate the structural, neurophysiological, and mediator mechanisms of the corticostriatal systems involved in the organization of behavior. Morphological studies of corticostriatal connections showed that along with the diffuse distribution of afferent terminals within the striatum, there were also elements of topical organization defined by anteroposterior and mediolateral gradients. Neurophysiological experiments on dogs and lower primates were used to study the spike activity of the prefrontal region of the cortex and the head of the caudate nucleus during training to conditioned first- and second-order reflexes and during the solution of complex problems involving delayed spatial selection. Studies demonstrated that while in dogs, most of the neurons recorded showed a transition to responses to the conditioned signal at a particular stage of carrying out a conditioned response, in monkeys all cells recorded showed specific responses at different periods of solving the task at all stages of the study. Neuropharmacological experiments on dogs showed that agents blocking glutamine receptors in the caudate nucleus had more pronounced effects at the phase of developing conditioned movement reflexes. Administration of these agents during the reflex reinforcement phase affected only the differentiation of inhibition. These results lead to the conclusion that the prefrontal area of the cortex and, to some extent, the caudate nuclei, act on incoming information specifying the current dominant need and the states of the external and internal environments, to carry out programmed actions and assess the results of these actions.     

Predicting performance during clinical years from the new Medical College Admission Test

The results of a predictive validity study of the new Medical College Admission Test (MCAT) using criteria from the clinical years of undergraduate medical education are presented and discussed. The criteria included course grades and faculty ratings of clerks in internal medicine, surgery, obstetrics and gynecology, pediatrics, and psychiatry; scores on a comprehensive test of clinical knowledge (including patient management type examinations); and scores on Part II of the examinations of the National Board of Medical Examiners (NBME). While the validity coefficients of the MCAT with the Part II examinations ranged from .03 to .47, they were higher than those of undergraduate grade-point averages with the same criteria. The implications of the small-to-medium size validity coefficients for admissions are discussed.     

Characterization and growth regulation of a rat intrahepatic bile duct epithelial cell line under hormonally defined, serum-free conditions

Bile duct epithelial cells, or cholangiocytes, proliferate in vivo under a number of pathologic (i.e., partial hepatectomy) and pathophysiologic (i.e., bile duct ligation, malignant transformation) conditions. However, little is known about the possible growth factors that modulate these proliferative responses, in part because an in vitro model to study proliferation of nontransformed, normal cholangiocytes is not available. We report here the development of a rat cholangiocyte cell line (MMRC, minimal media-requiring rat cholangiocytes) that grows under hormonally defined, serum-free conditions on plastic and maintains a cholangiocyte phenotype. Morphologic as well as functional studies indicate that the cell line is polarized and actively transports fluid and electrolytes in an apical to basolateral direction. MMRC, when cultured for 24 mo. and passaged 80 times, have not undergone malignant transformation, because the cell line failed to grow under anchorage-independent conditions or in nude mice. Cellular proliferation is accelerated 2-8-fold by insulin, insulin-like growth factor 1, epidermal growth factor, and hepatocyte growth factor, growth factors known to stimulate tyrosine kinase receptors, and inhibited 2-10-fold by TGFbeta and IL-2. Glyco-conjugates of primary (i.e., cholic and chenodeoxycholic acid) and secondary bile acids (i.e., deoxycholic and lithocholic acid) do not alter proliferation at low concentration (1 microM), but are toxic at higher concentration (10 microM). In summary, we have developed and characterized a cholangiocyte cell line derived from normal rat liver, which grows under hormonally defined, serum-free conditions, maintains a nonmalignant, cholangiocyte phenotype, displays morphologic and functional features of polarity, and alters its proliferation rate in response to a variety of growth factors.