Amphetamine increases extracellular concentrations of glutamate in the prefrontal cortex of the awake rat: a microdialysis study

OBJECTIVE: To determine if motion automated perimetry can identify early glaucomatous visual field defects in patients with suspected glaucoma (by disc), those with ocular hypertension, and those with primary open-angle glaucoma. METHODS: Motion automated perimetry, a foveally centered motion test, and standard visual field tests were conducted on one randomly selected eye of normal patients (n = 38), patients with suspected glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and patients with primary open-angle glaucoma (n = 21). Subjects' performance on both motion tests were compared with their performance on standard perimetry. RESULTS: Perimetric motion thresholds significantly distinguished the groups (P< or =.001), while the foveally centered motion test was unable to separate them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of those with suspected glaucoma, 27.8% of those with ocular hypertension, and 5.3% of the normal subjects had abnormal results on motion automated perimetry testing. Perimetric motion thresholds were significantly correlated with standard visual field thresholds (P< or =.001). CONCLUSION: Motion automated perimetry identifies visual field defects in patients who already show standard visual field loss as well as in a moderate percentage of those with suspected glaucoma and ocular hypertension, indicating that the testing of discrete locations might be necessary for increased diagnostic utility.     

Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study

OBJECT: To determine the extent and duration of change in extracellular glutamate levels after human traumatic brain injury (TBI), 17 severely brain injured adults underwent implantation of a cerebral microdialysis probe and systematic sampling was conducted for 1 to 9 days postinjury. METHODS: A total of 772 hourly microdialysis samples were obtained in 17 patients (median Glasgow Coma Scale score 5+/-2.5, mean age 39.4+/-20.4 years). The mean (+/-standard deviation) glutamate levels in the dialysate were evaluated for 9 days, during which the mean peak concentration reached 25.4+/-13.7 microM on postinjury Day 3. In each patient transient elevations in glutamate were seen each day. However, these elevations were most commonly seen on Day 3. In all patients there was a mean of 4.5+/-2.5 transient elevations in glutamate lasting a mean duration of 4.4+/-4.9 hours. These increases were seen in conjunction with seizure activity. However, in many seizure-free patients the increase in extracellular glutamate occurred when cerebral perfusion pressure was less than 70 mm Hg (p < 0.001). Given the potential injury-induced uncoupling of cerebral blood flow and metabolism after TBI, these increases in extracellular glutamate may reflect a degree of enhanced cellular crisis, which in severe head injury in humans appears to last up to 9 days. CONCLUSIONS: Extracellular neurochemical measurements of excitatory amino acids may provide a marker for secondary insults that can compound human TBI.     

Septal and hippocampal glutamate receptors modulate the output of acetylcholine in hippocampus: a microdialysis study

In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septum/vertical limb of the diagonal band (MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by using intracerebral microdialysis. Perfusion with N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an incrase in ACh output in the hippocampus. This increase was completely blocked by coadministration of their respective antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Perfusion in the MS/vDB with kainic acid also caused an increase in ACh output, but coadministration of CNQX attenuated the increase only partially. Perfusion with D-AP5 and CNQX alone in the septal probe did not affect ACh output from the hippocampus. In contrast to the results of septal administration of NMDA and AMPA, local perfusion with the same drugs in the hippocampus caused a decrease in ACh output. Whereas the results of septal administration of drugs indicate that septal cholinergic neurons probably receive excitatory glutamatergic innervation, the decrease in ACh output caused by administration of NMDA and AMPA in the hippocampus is poorly understood.     

Neuroprotective effects of lamotrigine in global ischemia in gerbils. A histological, in vivo microdialysis and behavioral study

A sudden surge in the release of glutamate is currently believed to be an important initiating step in neuronal damage due to an ischemic insult. In this experiment, we tested the efficacy of neuroprotection with lamotrigine, a novel antiepileptic drug that blocks voltage gated sodium channels and inhibits the ischemia-induced release of glutamate in the gerbil forebrain model of cerebral ischemia. The medication was administered 30 min before and 30 min after the insult in two groups of animals. Histological assessment of neuronal damage was evaluated at 7 and 28 days after the ischemic insult. Animals evaluated at 28 days also underwent behavioral testing. Microdialysis was used in the same model to study the response of ischemia-induced glutamate in saline treated controls versus animals treated with lamotrigine 20 min before the insult. There was highly significant neuronal protection in animals who were treated with lamotrigine either before or after the insult. Protection was seen both at 7 and 28 days after the insult. Behavioral testing also showed significantly better recovery in both sets of animals in comparison to the saline-treated group. Microdialysis confirmed a significant attenuation of the ischemia-induced glutamate surge when compared to the saline-treated animals. Our morphological, behavioral and microdialysis experiments show that lamotrigine offers significant neuroprotection from the effects of transient forebrain ischemia in gerbils. Neuroprotection with post-ischemic therapy probably depends on preserving the capacity of the sodium/calcium exchanger to reduce intracellular calcium concentrations or persistent 'toxicity' of glutamate in the reperfusion period on the already 'primed' injured neurons. These concepts need further study.     

Evidence for a striatal NMDA receptor modulation of nigral glutamate release. A dual probe microdialysis study in the awake freely moving rat

Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.     

Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.     

In vivo monitoring of gabapentin in rats: a microdialysis study coupled to capillary electrophoresis and laser-induced fluorescence detection

Gabapentin (GP) is a new anticonvulsant used in refractory epilepsy. Few studies have monitored the drug in vivo. We report the combination of capillary electrophoresis and laser-induced fluorescence detection (CZE-LIFD) with brain microdialysis and plasma ultrafiltration in an attempt to measure GP and offer an alternative technique for pharmacokinetic studies. We found that CZE-LIFD is capable of linearly measuring 10(-7)-10(-9) M GP in a 1 nL volume. It was also demonstrated that it is possible to monitor GP in prefrontal cortex dialysates and plasma in rats. It is concluded that the method permits in vivo monitoring of the drug in pharmacological as well as in clinical studies.     

Terminal transferase-dependent PCR: a versatile and sensitive method for in vivo footprinting and detection of DNA adducts

We report here a new, sensitive and versatile genomic sequencing method, which can be used for in vivo footprinting and studies of DNA adducts. Starting with mammalian genomic DNA, single-stranded products are made by repeated primer extension; these products are subjected to homopolymeric ribonucleotide tailing at the 3' termini with terminal deoxynucleotidyl transferase and then ligated to a double-stranded linker having a complementary 3' overhang, and used for PCR. This terminal transferase-dependent PCR (TDPCR) method can generate band signals many-fold stronger than conventional ligation-mediated PCR (LMPCR). A UV photofootprint in the mouse Xist gene promoter can be easily detected using TDPCR. No special enzymes or chemical reagents are needed to convert DNA adducts into strand breaks. Any lesion that blocks primer extension should be detectable.     

Serotonin 5-HT1A autoreceptor blockade potentiates the ability of the 5-HT reuptake inhibitor citalopram to increase nerve terminal output of 5-HT in vivo: a microdialysis study

The present study addressed the possibility that disinhibition of serotonin (5-HT) autoreceptor-mediated negative feedback might potentiate the elevation of nerve terminal 5-HT output induced by selective 5-HT reuptake blockade. To this end, rats were given citalopram and the 5-HT autoreceptor-blocking agents (S)-UH-301 (5-HT1A) and (-)-penbutolol (5-HT1A/1B), and the effect on extracellular 5-HT in the ventral hippocampus was monitored by means of in vivo microdialysis. Citalopram (5 mg/kg, s.c.) approximately doubled the 5-HT output, a response that was markedly augmented by (S)-UH-301 (3 mg/kg, s.c.) and (-)-penbutolol (8 mg/kg, s.c.) and by combined treatment with (S)-UH-301 (3 mg/kg, s.c.) plus (-)-penbutolol (1 microM; via the dialysis perfusion medium), but not by (-)-penbutolol (1 microM) alone. These findings provide evidence that 5-HT, in particular 5-HT1A, autoreceptor-mediated negative feedback mechanisms are pivotal in determining the nerve terminal 5-HT output level after 5-HT reuptake inhibition. These findings have important implications for the interplay between different processes controlling 5-HT transmission in vivo and might possibly offer a lead toward novel, therapeutically exploitable principles.     

Aging is associated with a decrease in synaptosomal glutamate uptake and an increase in the susceptibility of synaptosomal vitamin E to oxidative stress

We report a case of epithelioid leiomyosarcoma that developed on the nose of a 55-year-old Korean male over a one year period. The lesion was a pea sized, firm, erythematous, painless nodule with erosion in the center. Histologic examination revealed short spindled cells with blunt-ended nuclei and pleomorphic round to oval epithelioid cells with abundant eosinophilic cytoplasm that were perivascular and densely packed in the dermis. Immunostaining for desmin was negative, although stains for vimentin and smooth muscle actin were both strongly positive.     

Rumination, fear, and cortisol: An in vivo study of interpersonal transgressions.

The authors sought to examine whether rumination about psychologically painful, though nontraumatic, interpersonal transgressions is associated with increased salivary cortisol. They measured salivary cortisol, rumination about a transgression, fear and anger regarding the transgressor, perceived painfulness of the transgression, and positive and negative mood in 115 undergraduates who had experienced an interpersonal transgression during the previous 7 days. They obtained measurements on as many as 5 occasions separated by approximately 14 days each. On occasions when participants reported that they had been ruminating to a degree that was greater than was typical for them, they had higher levels of salivary cortisol than was typical for them. The rumination- cortisol association appeared to be mediated by fear of the transgressor. Rumination about even moderately painful but nontraumatic life events and associated emotions are related to biological changes that may subserve social goals such as avoiding social threats. Items from the rumination scale are appended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of the thyroid gland in the rat fetus in vivo. An ultrastructural and radioautographic study

A study of the differentiation of the thyroid follicles was carried out in rat fetuses between day 14 of pregnancy, when cellular polarization begins and day 18, when completely formed follicular lumina are differentiated. After day 18, only the shape and the size of the lumina undergo modifications. The mechanism of folliculogenesis involves the participation of several structures. At 14 days of pregnancy, adherens type contact zones with membrane densification appear between the cells. These junctional zones spread out and form infoldings which deeply penetrate the cytoplasm. Golgi vesicles migrate to these zones and they fuse among themselves and with the contact membranes : follicular cavities result which can be recognized as soon as day 16 of pregnancy. A radioautographic study showed the beginning of iodide organification at 17 days 11 hours of pregnancy. From this time onward silver grains were seen over the follicular cavity, even it is still incompletely formed.     

Somatosensory- and motor-evoked potential monitoring without a wake-up test during idiopathic scoliosis surgery. An accepted standard of care

STUDY DESIGN: This was a retrospective study of 500 patients undergoing corrective surgery between 1987 and 1997 for spinal deformity caused by idiopathic scoliosis. OBJECTIVES: To report the sensitivity and specificity of somatosensory-evoked and neurogenic motor-evoked potentials monitoring and the requirements for an intraoperative wake-up test for all idiopathic scoliosis surgeries at a single institution. SUMMARY OF BACKGROUND DATA: Intraoperative monitoring is recommended for use during corrective spinal surgery. Accepted monitoring standards and requirements for an intraoperative wake-up test are still debated. METHODS: The study group consisted of 500 patients undergoing corrective surgery for idiopathic scoliosis between 1987 and 1997. All patients were monitored using somatosensory-evoked and neurogenic motor-evoked potential techniques, using a standard protocol developed at this institution. RESULTS: The false-positive rate (significant data change without postoperative neurologic deficit) was 0.014% (n = 7). The true-positive rate (degradation of data that met warning criteria, with a corresponding postoperative neurologic deficit) was 0.004% (n = 2). No false-negative results (normal data during with a postoperative neurologic deficit) were seen. The sensitivity of combined somatosensory-evoked and neurogenic motor-evoked potential data in predicting neurologic status was 98.6%, and the specificity of normal data predicting normal findings in a neurologic examination was 100%. CONCLUSION: Combined somatosensory-evoked and neurogenic motor-evoked potentials monitoring during idiopathic scoliosis surgery represents a standard of care that obviates the need for an intraoperative wake-up test when reliable data are obtained and maintained.     

Release of dopamine, GABA and EAA in rats during intrastriatal perfusion with kainic acid, NMDA and soman: a comparative microdialysis study

There is an increasing amount of experimental evidence that excitatory amino acids (EAAs) are involved in the brain lesions observed after severe intoxication with the highly toxic organophosphorus compound soman. This study was undertaken to compare the acute actions of soman, and the glutamatergic receptor agonists kainic acid and N-methyl-D-aspartate (NMDA) on striatal release of dopamine and amino acids. The neurotoxic compounds were administered in high (10 mM) concentrations by unilateral intrastriatal microdialysis perfusion in freely moving rats. During the microdialysis the animals were observed for toxic signs related to convulsion. The glial fibrillary acidic protein (GFAP) was monitored as a marker of neurotoxicity in parts of prefrontal cortex, hippocampus, striatum and cerebellum. Acetylcholinesterase (AChE) inhibition in six brain regions was measured after soman perfusion in order to assess its cerebral distribution. We found that soman perfusion induced a major release of dopamine, GABA and aspartate in the striatum. Kainic acid also induced a release of dopamine and aspartate. NMDA was not as potent an inducer of striatal neurotransmitter release as soman and kainic acid. Soman and kainic acid perfusion produced convulsive behaviour in the rats. The main neurochemical event in the striatum during soman- and kainate-induced convulsions is the release of dopamine. We suggest that this major dopamine release might be as important as an increase in EAA in the cascade of pathological events leading to the brain damage in the striatum observed after soman intoxication.     

In vivo quantification of brain volumes in subcortical vascular dementia and Alzheimer''s disease. An MRI-based study

Ibuprofen is one of the most effective and widely used non-steroidal analgesic and anti-inflammatory agent. It is marketed as a racemic mixture though it is known that the pharmacological activity resides in the (S)-(+)-enantiomer only. Several direct/indirect liquid chromatographic methods involving a variety of chiral/achiral phases along with their possible role in resolution, chiral and achiral agents used for derivatisation have been discussed with special reference to ibuprofen, and mentioning their application to the resolution of other 2-aryl-propionic acids/profens.     

Gluconeogenesis in infancy and childhood. I. A method for the study of the in vivo gluconeogenesis from alanine and glycerol

The in vivo gluconeogenesis from alanine and glycerol in infants and children was studied by an isotope method, using 14C-labeled substates with subsequent separation of the radioactive compounds by thin-layer chromatography. Seven patients, aged 2 months to 2 years 11 months, with normal carbohydrate metabolism were studied. Trace amounts of [14C]alanine were injected intravenously in four fasting patients. The 14C moved quickly from alanine to lactate, with a peak activity in lactate obtained before 5 min. From 10 min on, the label disappeared rapidly from both. An equilibrium was established between alanine and lactate, displaced towards lactate. The peak activity in glucose was reached in 10-20 min, amounting to 10% of total injected activity. In one patient, who was also studied after a meal, the disappearance rate of alanine was reduced by 50%. Despite this reduction the appearance of label in lactate was increased, whereas the amount of label in glucose was much reduced. [14C]glycerol was injected intravenously in three fasting patients. In one patient, who received only a tracer dose of glycerol, 5 times more 14C appeared in glucose than in the patients studied with [14C]alanine. In two patients receiving a glycerol load together with the [14C]glycerol, the disappearance rate of glycerol was markedly reduced, as was the conversion of carbon to glucose and lactate.     

A comparison of hydroxyapatite-coated, titanium-coated, and uncoated tapered external-fixation pins. An in vivo study in sheep

OBJECTIVES: This study focuses on the relevance of size, eloquence, type of venous drainage, the Spetzler-Martin scale as a whole, and other factors, such as rupture of cerebral arteriovenous malformations (AVMs) for the prediction of neurological deficits in the context of microsurgical AVM removal. METHODS: One hundred and fifty patients with AVMs, whose data were retrieved from a prospectively employed computerised data bank were included. Seventeen patients (11.3%) underwent preoperative embolisation. According to the Spetzler-Martin scale they were graded as follows: 22.0% grade I, 32.0% grade II, 29.3% grade III, 14.0% grade IV, and 2.7% grade V. Intracerebral haemorrhage was present in 39.0%. The AVMs were <3 cm in 52.00/0, 3-6 cm in 43.3% and >6 cm in 4.7%; 59.3% of the AVMs were eloquently located and 29.3% had deep venous drainage (DVD). Follow up information was assessed 6 months after surgery in all but one patient, who died. The applied statistical test was chi2. RESULTS: Surgical morbidity was 15.3%. Early new deficits were noted in 39.3%, permanent new deficits in 10.6%, being significant (major) in 7.3%. The occurrence of permanent deficits correlated significantly with size, deep venous drainage, and the Spetzler-Martin scale. There was statistical evidence for a trend in risk of poor surgical outcome across the three categories non-eloquent, "less eloquent" (for example, visual cortex) and "highly eloquent" (brainstem, basal ganglia, or precentral cortex) with the last being associated with the highest risk for permanent neurological compromise. CONCLUSION: "Eloquence" of the Spetzler-Martin scale should be divided into "highly eloquent" and "less eloquent", which is important for risk analysis of the treatment of asymptomatic and deep seated AVMs and for future trials comparing various treatment modalities. In addition, resection of eloquent AVMs v non-eloquent ones is significantly associated with higher surgical morbidity.     

Plug closure of patent ductus arteriosus by transfemoral catheter method. A comparative study with surgery and a new technical modification

Plug closure of patent ductus arteriosus without thoracotomy is reliable and can be a good alternative to surgical closure for selected patients. We report our experiences with plug closure in 87 consecutive patients (age range, 3 to 38 years). Closure was successful in 83 patients (95 percent). There has been no mortality, and the failure in four patients (5 percent) was mainly due to an oversized ductus. A major complication during the procedure was dislodgment of the plug into either the aorta or the pulmonary artery, which occurred in five patients (6 percent). The late results were quite satisfactory, with no recurrence of shunting or any other complications. Comparison of these results with those of 100 patients treated surgically showed that the new catheter method did not seem to carry a higher risk but had certain advantages over thoracotomy. A simpler and less time-consuming method using a single catheter has been devised and successfully used in the most recent nine patients without failure. Simplification of the technique has signficantly reduced the time of the procedure and the dose of radiation.     

Effectiveness of vigabatrin against focally evoked pilocarpine-induced seizures and concomitant changes in extracellular hippocampal and cerebellar glutamate, gamma-aminobutyric acid and dopamine levels, a microdialysis-electrocorticography study in freely moving rats

Limbic seizures were evoked in freely moving rats by intrahippocampal administration of the muscarinic agonist pilocarpine via the microdialysis probe (10 mM for 40 min at 2 microl/min). This study monitored changes in extracellular hippocampal gamma-aminobutyric acid (GABA), glutamate and dopamine levels after systemic (30 mg/kg/day) or local (intrahippocampal or intranigral, 5 mM or 600 microM for 180 min at 2 microl/min) vigabatrin administration, and evaluated the effectiveness of this antiepileptic drug against pilocarpine-induced seizure activity. Extracellular GABA and glutamate overflow in the ipsilateral cerebellum was studied simultaneously. Microdialysis was used as an in vivo sampling technique and as a drug-delivery tool. Electrophysiological evidence for the presence or absence of seizures was recorded with electrocorticography. The observed alterations in extracellular hippocampal amino acid levels support the hypothesis that muscarinic receptor stimulation by the intrahippocampal administration of 10 mM pilocarpine is responsible for the seizure onset, and that the amino acids maintain the sustained seizure activity. The focally evoked pilocarpine-induced seizures were completely prevented by intraperitoneal vigabatrin premedication for 7 days or by a single intraperitoneal injection. Effective protection was reflected in a lack of sustained elevations of hippocampal glutamate levels. Rats receiving vigabatrin intrahippocampally or intranigrally still developed seizures, although there appeared to be a partial protective effect. During the intrahippocampal perfusion with 5 mM vigabatrin, extracellular hippocampal GABA levels increased, whereas the extracellular glutamate and dopamine overflow decreased. The lack of a complete neuroprotection after local vigabatrin treatment is discussed.     

The thermal effect of monopolar radiofrequency energy on the properties of joint capsule. An in vivo histologic study using a sheep model

BACKGROUND: Efforts to prevent and decrease tobacco use and tobacco-related disease include improving the quality of tobacco-control laws to make them more stringent in controlling tobacco advertising, youth access, and exposure to environmental tobacco smoke (ETS). However, because there are no instruments to empirically evaluate the quality of such laws, it has been difficult to demonstrate that their quality is associated with decreased youth access or tobacco-related morbidity. We present the first instrument for empirically assessing the quality of tobacco-control policies. METHODS: Recommendations for the content of an ideal, comprehensive tobacco-control policy were used as the 55 items in the Assessment of the Comprehensiveness of Tobacco Laws Scale (ACT-L Scale). Raters evaluated 71 tobacco-control laws with the scale; 70 of these were actual California laws and 1 was a model law from Americans for Non-smokers' Rights (ANR). RESULTS: Interrater (r = 0.64-0.89) and internal-consistency (r = 0.63-0.88) reliability of the scale and subscales were high, and validity was established by demonstrating that the ANR model law received a significantly higher total score (mean = 18.75) than all actual laws (mean = 2.04). California tobacco-control laws were poor in all areas (youth access, ETS, tobacco advertising). CONCLUSIONS: The ACT-L scale can be used to compare and evaluate the quality of tobacco-control laws, highlight areas in which further policy efforts are needed, quantify improvement in such policies, and empirically demonstrate the positive health impact of high-quality tobacco-control laws.