Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.

The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.     

Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.     

Quantitative DNA measurement by flow cytometry and image analysis of human nonseminomatous germ cell testicular tumors

Current clinical staging, which includes the use of serum tumor markers and imaging techniques, fails to identify the 30–40% of clinical stage I (CS I) nonseminomatous germ cell testicular tumor (NSGCT) patients who have occult metastatic disease. Therefore, there is a real clinical need to evaluate new biological parameters of the primary tumor that might be useful as predictors of occult metastatic disease. This study was undertaken to compare quantitative DNA measurements by flow cytometry and image analysis in CS I NSGCT, and to analyze the relevance of these parameters for predicting occult lymph node involvement. Different blocks of formalin-fixed, paraffin-embedded NSGCTs of 62 CS I patients who underwent retroperitoneal lymph node dissection between 1985 and 1989 were prepared according to the Hedley technique, and analyzed by quantitative cytometry. Thirty-six (58.1%) patients had histologically proven lymph node involvement (pathological stage II), whereas 26 (41.9%) patients (pathological stage I) had neither lymph node metastases according to retroperitoneal lymph node dissection (RPLND) specimens nor tumor recurrence during follow-up. Concordant results were found in 76.5% of the samples by both cytometric techniques. For flow cytometry, the percentages of aneuploid cells in the S- and the G2M+S-phase were the most robust predictive parameters for lymph node involvement, whereas for image analysis the 5c exceeding rate (5cER) had the most predictive significance. Based on the experience obtained in this study, both cytometric techniques provide additional information on tumor aggressiveness that might be useful in therapeutic selection of early stage NSGCT patients for either RPLND or surveillance only.     

Somatosensory evoked responses via electronic brain imaging (EBI).

This study of a series of 40 mildly head injured (concussed) patients suggests that different physiologic pathways underlying the tests done in a six-part resting EEG, and for the 11 evoked electrical potential shifts occurring in the cerebral terrain, are testable. Further work seems likely in order to ascertain which clinical signs and symptoms may be related to specific individual types of recorded electronic brain imaging (EBI) abnormality. Which of the 11 parameters studied, EEG, VER, AER, and SER, would be more or less likely to be abnormal in their individual patterns (as being deviant from normal controls) also remains to be defined. The relationship of these neurophysiologic abnormalities to certain postconcussive symptoms, i.e., headache, dizziness, blurred vision, etc., at this point in time remains to be evaluated more precisely. The authors suggest that further research is necessary in evaluating the clinical use of somatosensory evoked responses as an additional parameter in electronic brain imaging (EBI) technology.     

Immunological changes in normal pregnancy.

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.     

Iron deficiency anemia in children with exstrophy of the cloaca.

The clinical records of twenty-five children with exstrophy of the cloaca (EC) were retrospectively reviewed to evaluate the prevalence and the clinical characteristics of iron deficiency anemia (IDA). Five of the 25 children with EC (20 %) exhibited IDA at some point. Their ages at the time of diagnosis were between 1.9 and 13.0 years. In the four cases where IDA was thought to be related to iron malabsorption secondary to short-bowel syndrome, its treatment required longer periods of iron supplementation to correct the anemia and to restore the total body iron stores. Physicians caring for children with EC should monitor for and treat IDA as part of a comprehensive management plan.