Myocardial pharmacokinetics of thiopental in sheep after short-term administration: relationship to thiopental-induced reductions in myocardial contractility

The myocardial kinetics and dynamics of thiopental (750 mg over 2 min) were examined in chronically instrumented sheep (five studies in four sheep). The myocardial kinetics were studied by simultaneous rapid sampling of arterial and coronary sinus blood for 30 min. The myocardial kinetics for four of the five studies were best described by a single flow-limited compartment with apparent volumes of between 42 and 113 mL. These volumes equated to half-lives of equilibration between blood and myocardium of between 0.49 and 1.00 min when baseline blood flow was taken into account. The remaining study was better described by a model with a slight membrane limitation (permeability/flow ratio of approximately 2). Myocardial contractility was studied as a measure of myocardial pharmacodynamics and was reduced to 53% of baseline at approximately 2.5 min after the start of the dose. Effect compartment analysis showed that there was hysteresis between the time course of these contractility changes and the time course of the arterial concentrations, with effect compartment half-lives between 0.08 and 0.87 min. There was significantly less hysteresis for the coronary sinus concentrations. It is concluded that thiopental equilibrated rapidly with a component of the myocardium, and that consequently its effects on myocardial contractillity also rapidly equilibrated with both afferent and effluent myocardial blood.     

Assessment of pathophysiology of stroke by positron emission tomography

In stroke patients, multitracer positron emission tomography (PET) permits the assessment of acute changes in regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen consumption (rCMRO2) and glucose metabolism (rCMRgl), which are the initial steps in the complex molecular and biochemical process leading to ischaemic cell damage. While early infarcts exhibit low flow and oxygen consumption, increased oxygen extraction fraction (OEF) due to preserved metabolism at reduced flow suggests viability of tissue. However, most initially "viable" tissue will be metabolically deranged and will become necrotic in the further course; only in a few instances do these tissue compartments recover to normal function. Increased glucose uptake at reduced oxygen supply induces non-oxidative glycolysis with noxious lactacidosis, whereas hyperperfusion beyond the metabolic demand is of controversial effect. In subacute or chronic states after ischaemia reduced flow can be compensated by increased blood volume; when perfusional reserve is exhausted, oxygen extraction increases. Such findings may guide therapeutic decisions and predict the severity of permanent deficits. Functional deactivation of tissue remote from the lesion is found regularly as a sign of damaged connecting pathways. Flow and metabolic studies during the performance of specific tasks help to detect alternative functional loops and may yield prognostic information. Repeat studies in the course of stroke are employed for the evaluation of therapeutic strategies targeted to improve reperfusion or to effect metabolic or biochemical alterations. In the future PET may gain additional clinical importance when patients are selected for elective treatment according to the prevailing pathophysiological pattern.     

Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole

OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).     

Impulsive and compulsive self-injurious behavior in bulimia nervosa: prevalence and psychological correlates

Acute ischemia in the complete territory of the carotid or the middle cerebral artery may lead to cerebral edema with raised intracranial pressure and progression to coma and death. Although clinical data suggest benefit for patients undergoing decompressive surgery for massive space occupying hemispheric stroke, little data about the effects of this procedure on morbidity and outcome is available. The experimental data support an early surgical approach. For early and probably most effective treatment of severe, space-occupying cerebral ischemia, the "malignant" character of the brain edema has to be recognized early after onset of vessel occlusion. Hereby magnetic resonance imaging (MRI) may allow to determine the clinical significance of brain edema early after onset, simultaneously allowing to monitor the evolution of ischemia. We performed serial SE-MRI in rats with acute hemispheric infarctions treated by decompressive craniectomy. Focal cerebral ischemia was induced in 36 rats using an endovascular occlusion technique. Decompressive craniectomy was performed 4 and 24 hours after vessel occlusion in groups of 12 animals each. Twelve animals were not treated by decompressive craniectomy (control group). Four, 24, 48, 72 and 168 hours after MCAO all animals were examined with conventional T1- and T2-weighted SE-MRI. Shift of the midline structures and compression of the ventricles were scored. Changes in weight and neurological performance were measured daily. The infarction volume was calculated by triphenyltetrazolium chloride staining 168 hours after MCAO. While mortality in the untreated group was 33.3%, none of the animals treated by a decompressive craniectomy died (mortality 0%). Neurological behaviour, weight loss and infarction volume were significantly better in the animals treated by early decompressive craniectomy (p < 0.05). Four hours after MCAO all untreated animals showed a massive shift of the midline structures and a massive compression of the ventricles; only 7 of 12 animals treated early by craniectomy showed mild mass effects. Correlation of the histological brain damage with T2-weighted MRI 4 hours after MCAO was poor (r = 0.41); later than 24 hours there was a good correlation (r > 0.7). Our results suggest that decompressive craniectomy in malignant cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. In the acute phase of hemispheric infarction conventional SE-MRI is not sensitive in estimation of infarction size. Later than 24 hours, conventinal SE-MRI proved to be useful in monitoring brain edema and infarction size in this rat model of malignant hemispheric stroke.     

Egg handling and storage

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.     

Monitoring aortic root effluent during retrograde cardioplegia delivery

Early signs of brain infarction can be detected by modern CCT technology even within the first 6 h after stroke. Little is known about the prognostic significance of early infarction signs in CCT. We prospectively evaluated clinical and CCT findings of 95 consecutive patients with an acute ischemia in the territory of the middle cerebral artery. All patients were admitted to our stroke unit within 6 h after stroke. In 55 patients CCT was performed within 3 h, and in 40 cases between 3 and 6 h. In all patients the clinical findings were assessed by the Scandinavian Stroke Scale (SSS). The disability due to stroke was evaluated after 4 weeks by use of the modified Rankin Scale. We could demonstrate the following early signs of cerebral infarction: focal hypodensity (23.2%), obscuration of basal ganglia (12.6%), focal brain swelling (22.1%), hyperdense middle cerebral artery sign (HMCA; 11.5%). In 3 patients early edema led to ventricular compression, in 1 patient to midline shift. The occurrence of early infarction signs did not depend on the etiology of ischemia but was significantly associated with a severe neurological deficit at admission and an unfavourable disability status 4 weeks after stroke. Focal brain swelling and HMCA were often followed by extensive infarction lesions on the follow-up CCT. In conclusion, early signs of hemispheric brain infarction visible on CCT scans performed within 6 h after stroke are correlated with severe stroke and an unfavourable functional outcome. However, a substantial part of our patients had a benign course of the disease in spite of early CCT pathology. Decisions on therapy in individual patients therefore should not depend on early CCT findings exclusively.     

Perfusion-MRI in cerebral infarct

PURPOSE: To investigate the hemodynamic changes in patients with acute cerebral stroke by perfusion MRI. MATERIAL AND METHODS: In 12 patients with acute stroke in the territory of the middle cerebral artery, perfusion MRI was performed. Peak time, mean transit time, regional cerebral blood volume and regional cerebral blood flow were calculated in the infarction, the peri-infarction area and the contralateral hemisphere. RESULTS: In the infarction the mean blood flow was 29 ml/100 g/min, compared to about 40 ml/100 g/min in the peri-infarction area and the contralateral hemisphere. In two patients increased cortical blood flow was found in the infarction due to luxury perfusion. The cerebral blood volume was reduced in the infarction, but significantly increased, to 7.3 ml/100 g, in the peri-infarction tissue. CONCLUSION: Perfusion MRI allows one to differentiate various patterns of perfusion disorders in patients with acute cerebral stroke. The resulting data may be helpful in describing the pathophysiologic mechanisms of compensation.     

Clinical characteristics of motor deficit in patients after hemispheric stroke]

Correlation between clinical structure of motor deficit and indices of stimulation electromyography was studied in 108 patients with hemispheric stroke. Methods of statistic analysis were applied including devising of histograms, Pareto diagrams, determination of the narrowness of correlation ratio. The analysis revealed complex relationship between the signs of motor deficit in clinical picture and the data of stimulation electromyography in patients with cerebral hemispheric stroke.     

Effects of hemodilution on splanchnic perfusion and hepatorenal function. I. Splanchnic perfusion

Perfusion of intestinal organs increases in response to acute normovolemic hemodilution (ANH). However, detailed studies on distribution of regional splanchnic organ perfusion during ANH are lacking. We therefore carried out this study to test the hypothesis that ANH does not cause disturbance of physiologic patterns of regional splanchnic organ blood flow. After governmental permission, 22 anesthetized dogs were instrumented to allow invasive hemodynamic measurements and intracardial injection of radioactive microspheres (diameter 15 micro m) for determination of regional organ perfusion. Measurements were made at baseline (hematocrit 37 +/- 3%) and after ANH with 6% hydroxyethyl starch (mol. wt. 200000 / 0.5) to hct 20 +/- 1%. After completion of the protocol, splanchnic organs were removed and dissected into small samples according to anatomical and functional principles. Regional perfusion was determined based on the microsphere content of each sample. Hepatic, intestinal, and pancreatic blood flow increased with ANH. Hepatic arterial blood flow rose by 86%, whereas portal venous perfusion increased by 28%. Small intestine mucosal perfusion was augmented by 68% while the non-mucosal tissue compartment of the gut wall received 32% more blood flow after ANH which is in proportion to the increase in cardiac index after ANH. This redistribution of intestinal flow might be the basis for the preservation of tissue oxygenation during moderate isovolemic anemia.     

Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype

BACKGROUND and PURPOSE: Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke. METHODS: We prospectively examined 297 patients (mean age, 72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis. RESULTS: We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables. Conclusions-Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.     

Flow cytometric analysis of variations in the DNA content of superficial and deep layers in colorectal cancer

Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether chronic or acute changes in tumour perfusion necessarily lead to changes in tissue oxygenation and bioenergetic status since, as a rule, blood flow is thought to be the ultimate determinant of the tumour bioenergetic status. Based on this study, there is clear experimental evidence that growth-related or acute (following i.v. administration of tumour necrosis factor alpha) decreases in tumour blood flow are accompanied by parallel alterations in tissue oxygenation. In contrast, tumour energy status remains stable as long as flow values do not fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the main substrate can be recruited from the enlarged interstitial compartment. Perfusion rate seems to play a paramount role in determining energy status only in low-flow tumours or low-flow tissue areas.     

Hibernating myocardium and the 'no reflow' phenomenon: a study of absolute regional myocardial perfusion and glucose metabolism using positron emission tomography in chronic and acute heart disorders

Positron emission tomography (PET) is a powerful tool for in vivo measurements of physiologic processes such as regional myocardial blood flow and metabolism. Myocardial blood flow is often studied using radioactive labeled ammonia (13NH3) while myocardial metabolism can be investigated using 18F-fluorodeoxyglucose (FDG). Moreover, the use of appropriate kinetic models allows quantification of these processes. In this study, myocardial viability in both chronic and acute heart disease was investigated by the use of positron emission tomography. In this context, viable refers to dysfunctioning areas of the myocardium in which functional recovery is observed after revascularization. In patients suffering chronic coronary artery disease, PET findings of flow and metabolism were correlated with myocardial ultrastructure. In dysfunctional myocardial segments, normal 13NH3 uptake or decreased 13NH3 uptake with relatively increased FDG uptake (PET mismatch) indicates the possibility for functional recovery after bypass surgery. Since absence of scar tissue in these segments is likely to be required for functional recovery, it was not surprising that little fibrosis was found in myocardial biopsies taken in PET mismatch areas. The biopsies also revealed the presence of viable myocardial cells showing a variable loss of contractile material. The contractile material was replaced by glycogen. One could wonder about the time course needed for functional recovery after restoration of blood flow in the presence of a considerable amount of cells lacking a normal contractile apparatus. It would therefore be interesting to study functional recovery at different time points in patients with variable amounts of these myolytic cells. Probably, recovery of contractility would be slower in myocardial areas with a larger amount of abnormal cells. Another question that arises is the meaning of the increased FDG signal in dysfunctional, though viable myocardium. At first sight, glycogen storage in myolytic cells seems an excellent candidate to explain the increased intake of FDG in PET mismatch areas. However, in this study, in areas considered nonviable by PET, similar amounts of myolytic cells were found. Histologically altered cells might represent a structural and protective adaptation to long term hypoperfusion or to repetitive episodes of ischemia. Another possibility for the increased FDG uptake is an enhancement of glucose utilization in the mismatch areas not only in the myolytic cells, but also in the morphologically normal cell fractions. In patients with a PET mismatch pattern, significant recovery of flow and function was observed after surgery with a significant decrease in glucose utilization. Although it would have been interesting to histologically study the fate of myolytic cells in these recovered areas, this was not possible for obvious ethical reasons. In areas considered non viable by PET expressing a concordant decrease of 13NH3 and FDG uptake (PET match), no recovery of function, flow or metabolism was noted at follow-up. Another study was conducted in our department in infarct patients in which regional myocardial blood was measured within 24 hours after successful thrombolysis. The aim was to investigate the presence of impaired tissue perfusion in the acute stage and to evaluate its effect on recovery of flow, metabolism and function. In about 30% of patients with a TIMI 3 patent vessel, seriously impaired tissue flow was observed in the acute stage. Whether this impairment was due to irreversible damage to capillaries or myocytes, to reperfusion injury or to the presence of multiple distal thrombi remains unknown. Most patients showing severely impaired regional myocardial blood flow in the acute stage revealed absence of viable myocardium on follow-up PET NH3/FDG scans.     

Terminal nitrogen rise

Eighteen-breath nitrogen washouts were performed on eight subjects. Each washout could be simulated by a four-compartment model, each compartment with a different ventilation-to-volume ratio and a variable contribution to expiratory flow. In large breaths initiated near residual volume, a terminal nitrogen rise (TNR) was seen. To account for the TNR with this model, there were relatively small changes in flow from compartments with markedly different nitrogen concentration. Reasons are given for believing these compartments could not be the upper and lower lung. Three of these subjects were studied in the supine, seated, and head-down positions. The TNR was seen at the same lung volume in all positions. At routine bronchospirometry in a second group of subjects, sampling with small catheters during a nitrogen washout showed a TNR in the expirate of lungs, lobes, segments, and subsegments in the upright and supine positions. Apparently a large vertical hydrostatic gradient is unnecessary to produce a TNR. Finally, the TNR was shown to occur at that lung volume where transpulmonary pressure is very small and changing rapidly with volume. This TNR was often followed by a terminal nitrogen fall while the lung was continuing to empty. The TNR occurs when flow from a large poorly ventilated compartment increases relative to the flow from other compartments. A model of lung in which the poorly ventilated compartment develops high specific compliance at low lung volume explains these data.     

Safety and efficacy of spinal vs general anaesthesia in bone marrow harvesting

In cases of completed middle cerebral artery territory stroke, prognosis is very poor and the clinical course is characterised by a rapid decline in consciousness and signs of herniation 2-4 days after the onset of symptoms due to a space-occupying mass. Failure of conservative therapy is the rule, and herniation is the usual cause of death, occurring in almost 80 per cent of cases. Recently published results have suggested that hemicraniectomy may improve survival in patients with massive hemisphericstroke, decreasing mortality to less than 35 per cent. The article presents what is probably the first case to be reported in Sweden, where hemicraniectomy was performed on a 45-year-old woman with right hemispheric completed middle cerebral artery infarction.     

The accuracy of substituted judgments in patients with terminal diagnoses

The effect of the molecular weight of polymer powders and the polymer powder/liquid ratio on the viscoelastic properties after gelation of tissue conditioners was studied by means of a stress relaxation test. The results are summarized as follows. The lower-molecular-weight polymer powders produced the larger flow after gelation especially at long times. The use of a lower powder/liquid ratio produced a greater flow after gelation at both short times and long times. The difference in the molecular weight of polymer powders and the powder/liquid ratio was found to have no influence on changes in viscoelastic properties with the passage of time. It would be possible to control the viscoelastic properties of tissue conditioners suitable for each clinical purpose by making variations in composition and structure.     

Staphylococcal vertebral osteomyelitis: case report

A 65-year old male Saudi patient presented with rapidly progressive quadriparesis. Lower cervical myelopathy was associated with radiological features of bone destruction, inflammatory disease of the spine and a paravertebral mass. Although tuberculosis and brucellosis are more commonly responsible for this clinical picture in our practice, Staphylococcus aureus was isolated from tissue recovered at surgery. He has been followed up for 12 months and has made an almost complete recovery after surgical decompression of spinal cord and a 2-month course of intravenous flucloxacillin. This case underscores the need for tissue diagnosis in patients presenting with inflammatory paravertebral swellings even in areas endemic for tuberculosis and brucellosis.     

Effects of injection rates of contrast material on arterial phase hepatic CT

PURPOSE: The aim of our study was twofold: to determine the frequency and magnitude of perfusion defect in stroke patients who qualify for rtPA therapy within 3 hours of stroke onset and to determine the ability of rtPA to improve perfusion by 24 hours. SUBJECTS AND METHODS: Patients with suspected hemispheric stroke who fulfilled entry criteria into the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study and also had pretreatment injection of (99m)Tc-HMPAO, with single-photon emission computed tomography (SPECT) performed using a triple-head camera at baseline and 24 hours, were included. RESULTS: All 12 patients who qualified for rtPA therapy had perfusion defects on baseline SPECT (SPECT graded scale [SGS] score range, 16 to 79). Mean+/-SD perfusion defect was comparable in rtPA (n=4)versus placebo (n=5) groups (SGS score, 36+/-18 versus 39+/-12; NS) despite earlier injection time in the rtPA group (98+/-24 versus 141+/-21 minutes; P=.02). Total SPECT scanning time was 20 to 25 minutes. At 24 hours, reperfusion was greater in rtPA patients compared with the placebo group (SGS score, 7+/-9 versus 29+/-17; P=.05), with relative improvement in the region-of-interest scores of 87+/-16% after rtPA compared with 28+/-30% with placebo (P=.01). CONCLUSIONS: A substantial perfusion defect exists in stroke patients with larger hemispheric infarcts who meet NINDS criteria for rtPA therapy, and rtPA is better able than placebo to rectify this defect. SPECT is feasible for clinical trials and should be evaluated as a substituted end point in stroke therapeutic trials.     

Changes in muscle blood flow distribution during hyperthermia

Blood flow is a critical parameter for obtaining satisfactory temperature distributions during clinical hyperthermia. This study examines the changes in blood flow distribution in normal porcine skeletal muscle before, during and after a period of regional microwave hyperthermia. The baseline blood flow distribution during general anaesthesia and after the insertion of the thermal probes was established independently in order to isolate the changes due to hyperthermia. General anaesthesia alone and thermocouple insertion during anesthesia had no significant effect on the muscle blood flow distribution. Regional microwave heating generated a non-uniform blood flow distribution which was a function of the tissue temperature distribution. Blood flow was greater in those tissues samples in which higher temperatures were recorded and less in those sampled further from the applicators peak SAR (Specific Absorption Rate). The increase in blood flow appears to be primarily a local phenomenon. Although muscle blood flow may be considered to be uniform prior to heating, this does not hold during hyperthermia treatment. Therefore, the non-uniform nature of the blood distribution during heating should be incorporated into any practical bioheat transfer model.     

Important points in therapy of pulmonary tuberculosis and atypical mycobacterium respiratory infections

PURPOSE: Our goal was to elucidate the temporal profile of cerebral circulation and its relationship to prognosis in patients with diffuse brain injury by using single-photon emission CT (SPECT) and 123I-iodoamphetamine (IMP). METHODS: A total of 67 assessments were made in 26 patients with diffuse brain injury (Glasgow Coma Scale score < or = 8). The microsphere method was used for quantifying cerebral blood flow (CBF). The hemispheric CBF was defined as a mean regional CBF (rCBF), and the total cerebral hemispheric CBF (tCBF) as a mean of the bilateral hemispheric CBF. The relationship between patient outcome and tCBF was investigated. RESULTS: The rCBF in patients with diffuse brain injury showed dynamic and global changes with little regional differences. The tCBF values increased in 1 to 3 days, and they were higher in the poor-outcome group than in the good-outcome group. During the period of 14 to 42 days, the tCBF values stayed within normal range in the good-outcome group, whereas they were below normal range in the poor-outcome group. CONCLUSION: Our results revealed a good correlation between patient outcome and CBF values. Quantitative and sequential CBF studies with IMP SPECT are promising for helping to determine the prognosis for patients with diffuse brain injury.     

The weanling male rat as an assay for endocrine disruption: preliminary observations

Kelce and Wilson (J. Mol. Med. 75, 198-207, 1997) have suggested that dosing chemicals to newly weaned male rats for 1 month may yield a useful assay for antiandrogens. This suggestion was supported by reference to unpublished data on the antiandrogen vinclozolin which indicated reductions in the weight of accessory sex organs. The necessity for dosing during the full approximately 30 days of the protocol was not justified. An evaluation of this protocol has commenced by the dosing of vinclozolin, cyproterone acetate, and anastrozole daily to newly weaned male rats for 3, 7, or 14 days. No changes were observed in accessory sex organs when vinclozolin or anastrozole was dosed for 3 days. Significant changes were observed in the absolute and relative weight of all of the sex accessory organs for rats dosed for 7 or 14 days with cyproterone acetate. The effects produced by vinclozolin and anastrozole when dosed for 7 or 14 days varied according to the duration of exposure with the main effects on the accessory sex organs being seen after 14 days of dosing. The effects produced after 7 days of dosing with vinclozolin or anastrozole in arachis oil had resolved 10 days after the last of the seven doses. Data are presented using either hydroxy propyl methyoxycellulose (HPMC) or arachis oil as vehicle, the former being recommended for general use. These preliminary results are encouraging, and the evaluation of the second 2 weeks of the suggested 30-day protocol is proceeding. Concurrent control data indicate that the relative weight of the liver, testes, and epididymides increases over the first 14 days post-weaning, while those of the kidney, the seminal vesicles, and prostate decrease. These changes in relative tissue weight were much less than the increase in relative weight of the uterus observed in female animals at puberty. That indicates that successful use of a final version of this assay will depend on access to inhouse control tissue weight data and the use of appropriate animal group sizes. These preliminary data are presented to reduce duplication of effort in this rapidly expanding area of toxicology.