Time-Reversal Measurement of the p-Wave Cross Sections of the

The cross sections of the ^{7}Be(n,α)^{4}He reaction for p-wave neutrons were experimentally determined at E_{c.m.}=0.20-0.81 MeV slightly above the big bang nucleosynthesis (BBN) energy window for the first time on the basis of the detailed balance principle by measuring the time-reverse reaction. The obtained cross sections are much larger than the cross sections for s-wave neutrons inferred from the recent measurement at the n_TOF facility in CERN, but significantly smaller than the theoretical estimation widely used in the BBN calculations. The present results suggest the ^{7}Be(n,α)^{4}He reaction rate is not large enough to solve the cosmological lithium problem, and this conclusion agrees with the recent result from the direct measurement of the s-wave cross sections using a low-energy neutron beam and the evaluated nuclear data library ENDF/B-VII.1.

Stiff-man syndrome. Report of a case.

Stiff-man syndrome is a well-described, but rare and often overlooked, neuromuscular syndrome of rigidity, spasm, and gait abnormality that is associated with several endocrinologic and autoimmune disorders. A patient exhibiting many typical features of stiff-man syndrome had intermittent symptoms for 22 years before the correct diagnosis was made. Similar to many described patients, she was diabetic, hyperthyroid, and had elevated islet cell, antithyroid, and glutamic acid decarboxylase antibody levels. The high frequency of diabetes mellitus among patients with stiff-man syndrome is emphasized, as is increasing evidence to suggest that elaboration of anti-glutamic acid decarboxylase and anti-islet cell antibodies may play a role in the pathophysiologic state of the disorder.

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Blood flow responses to deep brain stimulation of thalamus.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) provides remarkable relief of tremor in the limbs contralateral to the side of the brain stimulated. The benefits have been sufficiently dramatic that this is now an accepted clinical treatment of essential as well as other forms of tremor. Despite this clinical benefit, the mechanism of action of DBS remains unknown. In this investigation, we sought to determine the effects of VIM DBS on neuronal function. METHODS: The authors used PET measurements of qualitative regional cerebral blood flow in patients with essential tremor to determine the effects of DBS in the left VIM. Each subject had four to six scans with the arms at rest and DBS turned either on or off during alternate scans. Continuous physiologic monitoring revealed no tremor during any of the scans. The PET images from each subject were aligned, averaged, and coregistered to a standard image oriented in stereotactic space. RESULTS: The authors used subtraction image analysis with statistical parametric mapping methods and a restricted volume search to identify a significantly increased flow response at the site of stimulation in thalamus. An exploratory analysis revealed increased flow in ipsilateral supplementary motor area, a region that receives afferents from VIM. CONCLUSIONS: The increased blood flow at terminal fields of thalamocortical projections suggests that DBS stimulates and does not inactivate projection neurons in VIM thalamus.

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior.

In a double-blind, prospective study, 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression, agitation, and assaultive behavior. Although lorazepam and haloperidol produced an equivalent mean decrease in aggression, significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients; this effect was independent of sedation. Lorazepam produced significantly fewer extrapyramidal symptoms. These data support the current clinical practice of using lorazepam (alone, or in combination with a neuroleptic) for control of acute aggressive and assaultive behavior.

The treatment of autonomic dysfunction.

Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs.

Serotonin, dopamine, and motor effects in Parkinson's disease.

We review recent reports suggesting that use of selective serotonergic agents that either inhibit synaptic reuptake or have specific serotonin receptor affinities may benefit a variety of motor disturbances in Parkinson's disease. The complex, mixed motoric effects of these agents in Parkinson's disease have not allowed for a consistent view on the interrelationship between dopamine and serotonin (5HT) in motor control but may speak to the nature of dysregulated neurotransmission in the disease.

Motor complications of chronic levodopa therapy in Parkinson's disease.

We report on motor complications of chronic levodopa therapy among 811 levodopa-responsive patients with idiopathic Parkinson's disease (PD), stratified by duration after diagnosis. Predictable "offs" were noted in 20.2% of patients in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and early morning dystonia were less common. Longer duration was associated with greater percentages of patients with off periods or dyskinesias (up to 70% after 15 years), although patients with 6-15 years' duration saw relatively little increase in frequency of those complications, and a minority of patients (approximately 30%) with duration into the second decade did not experience off periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era. We note that with advancing PD duration, levodopa complications are more common, but in many cases there appear to be relatively stable periods in terms of levodopa dosage and disease severity, and a minority of patients will be relatively free of motor complications into the second decade of their disease.

Critical period for adverse effects on development of reproductive system in male offspring of rats given di-n-butyl phthalate during late pregnancy.

The objective of this study was to determine the susceptible days for the adverse effects of di-n-butyl phthalate (DBP) on development of reproductive system in male offspring following maternal administration on successive 3-day period during late pregnancy. Pregnant rats were given DBP by gastric intubation at 1000 or 1500 mg/kg on days 12-14 or 18-20 of pregnancy or at 500, 1000 or 1500 mg/kg on days 15-17 of pregnancy. A significant decrease in the maternal body weight gain and/or food consumption was found in the DBP-treated groups regardless of the days on which DBP at 1000 and 1500 mg/kg was given. A significant increase in the number of resorptions per litter was found in the groups given DBP at 1500 mg/kg on days 12-14 and 15-17 of pregnancy. The weights of male and female fetuses were significantly decreased in the groups given DBP at 1000 and 1500 mg/kg on days 12-14 and 18-20 and at 1500 mg/kg on days 15-17. A significant increase in the incidence of fetuses with undescended testes was found at 1500 mg/kg on days 12-14 and at all doses on days 15-17. A significant decrease in the anogenital distance (AGD) of male fetuses was observed in the groups treated with DBP regardless of the days of treatment. The AGD/body weight ratio in male fetuses was significantly reduced in the groups given DBP on days 15-17, but neither on days 12-14 nor 18-20. The AGD of female fetuses in the DBP-treated groups was comparable to that in the control group. It was concluded that period of days 15-17 of pregnancy was the most susceptible for DBP-induced undescended testes and decreased AGD in male offspring.

Adverse effects of diphenyltin dichloride on initiation and maintenance of pregnancy in rats.

The objective of this study was to characterize the adverse effects of diphenyltin dichloride (DPTCl) during early pregnancy. Following successful mating, female rats were given DPTCl by gastric intubation at 0, 4.1, 8.3, 16.5, 24.8 or 33.0 mg/kg on days 0-3 or days 4-7 of pregnancy. Female rats were sacrificed on day 20 of pregnancy and pregnancy outcome was determined. The pregnancy rate was significantly decreased after administration of DPTCl on days 0-3 at 24.8 mg/kg and on days 4-7 at 33.0 mg/kg. The incidence of preimplantation loss was significantly increased after administration on days 0-3 at 16.5 mg/kg and above and on days 4-7 at 33.0 mg/kg. In females having implantations, the numbers of implantations and live fetuses and the incidences of pre- and postimplantation loss in the groups given DPTCl on days 0-3 were comparable to the controls. The incidence of postimplantation loss was significantly increased after administration of DPTCl on days 4-7 at 33.0 mg/kg. A pair-feeding study revealed no evidence of pre- and postimplantation embryolethality induced by food restriction. It could be concluded that DPTCl during early pregnancy causes early embryonic loss and DPTCl has greater effects on reproduction when administered during earlier than later stages of blastogenesis.

Further evaluation of developmental toxicity of di-n-butyl phthalate following administration during late pregnancy in rats.

The objective of this study was to further evaluate the developmental toxicity of di-n-butyl phthalate (DBP) administered during the second half of pregnancy. Pregnant rats were fed a diet containing DBP at a dose of 0 (control), 0.5, 1.0 or 2.0% ad libitum on days 11-21 of pregnancy. Average daily intakes of DBP were 331, 555 and 661 mg/kg for the 0.5, 1.0 and 2.0% groups, respectively. No significant changes induced by DBP were detected in the incidence of postimplantation loss and numbers of live fetuses and of resorptions and dead fetuses. The weights of male and female fetuses at 2.0% DBP were significantly decreased. The incidences of fetuses with cleft palate and fetuses with fusion of the sternebrae at 2.0% DBP and fetuses with undescended testes at 1.0 and 2.0% DBP were significantly increased. There were significant decreases in the anogenital distance (AGD) of male fetuses in the 1.0 and 2.0% DBP groups, also. AGD of female fetuses in the DBP-treated groups was comparable to that in the control group. It was concluded that DBP administered during the second half of pregnancy produced adverse effects on the reproductive development in male fetuses.

Developmental toxicity of mono-n-benzyl phthalate, one of the major metabolites of the plasticizer n-butyl benzyl phthalate, in rats.

Mono-n-benzyl phthalate (MBeP), one of the major metabolites of the plasticizer n-butyl benzyl phthalate, was evaluated for developmental toxicity in Wistar rats. Rats were given MBeP by gastric intubation at 0, 250, 313, 375, 438 or 500 mg/kg from day 7 through day 15 of pregnancy. Significant decreases in the maternal body weight gains and food consumption during administration period were observed at 313 mg/kg and above and at 250 mg/kg and above, respectively. Significant increase in the incidence of postimplantation loss per litter was found at 438 and 500 mg/kg. The incidences of fetuses with external malformations at 438 mg/kg, of fetuses with skeletal malformations at 313 mg/kg and above and of fetuses with internal malformations at 375 mg/kg and above were higher than those in the control group. Defects in the cervical and thoracic vertebrae, ribs and kidney were frequently observed.

Developmental toxicity evaluation of phthalic acid, one of the metabolites of phthalic acid esters, in rats.

The objective of this study was to evaluate the developmental toxicity of phthalic acid (PA), which is one of the metabolites of phthalic acid esters (PAEs). Pregnant rats were given PA at a dose of 0 (control), 1.25, 2.5, or 5.0% in the diet on day 7 through day 16 of pregnancy. Average daily intakes of PA were 1021 mg/kg for the 1.25% group, 1763 mg/kg for the 2.5% group, and 2981 mg/kg for the 5.0% group. Maternal toxicity occurred in the 2.5 and 5.0% groups as can be seen by significant decreases in the maternal body weight gain and food consumption during the administration period. No significant changes in maternal parameters were found in the 1.25% group. Neither deaths nor clinical signs of toxicity were noted in any groups. No significant changes induced by PA were detected in the incidence of postimplantation loss and number and sex ratio of live fetuses. Significant decreases in the weight of male fetuses and number of ossification center of the caudal vertebrae were found in the 5.0% group. Morphological examinations of fetuses revealed no evidence of teratogenesis. Thus it appears unlikely that PA may be responsible for the production of the developmental toxicity of PAEs.

Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late pregnancy.

The objective of this study was to determine the adverse effects of monobutyl phthalate (MBuP), a major metabolite of dibutyl phthalate (DBP), on development of the reproductive system in offspring following maternal administration during late pregnancy, and to assess the role of MBuP in the antiandrogenic effects of DBP. Pregnant rats were given MBuP by gastric intubation at 250, 500, or 750 mg/kg on days 15 through 17 of pregnancy. Maternal body weight gain and food consumption during the administration period were significantly decreased at 500 mg/kg and higher and at 750 mg/kg, respectively. A significant increase in the incidence of postimplantation embryonic loss was found at 500 mg/kg and higher. The body weights of male and female fetuses were significantly lower at 750 mg/kg. A significant increase in the incidence of fetuses with undescended testes was found at 250 mg/kg and higher. A significant decrease in the anogenital distance (AGD) of male fetuses was observed at 250 mg/kg and higher. The AGD/body weight ratio and AGD/cube root of body weight ratio in male fetuses was also significantly reduced at 250 mg/kg and higher. The AGD, AGD/body weight ratio and AGD/cube root of body weight ratio in female fetuses in the MBuP-treated groups were comparable to those in the control group. The present study indicates that MBuP on days 15 to 17 of pregnancy produced adverse effects on the development of reproductive system in male offspring and suggest that MBuP may be responsible for the induction of the antiandrogenic effects of DBP.

Effects of monobutyl phthalate on reproductive function in pregnant and pseudopregnant rats.

The effects of monobutyl phthalate (MBuP) on reproductive function were determined in pregnant and pseudopregnant rats. Rats were given MBuP by gastric intubation at 250, 500, 750, or 1000 mg/kg on days 0 to 8 of pregnancy and pregnancy outcome was determined on day 20 of pregnancy. The effects of MBuP on the uterine function, as a cause of early embryonic loss, were also determined in pseudopregnant rats, with an induced decidual cell response. The same doses of MBuP were given to pseudopregnant rats on days 0 to 8 of pseudopregnancy and the uterine weight on day 9 served as an index of uterine decidualization. MBuP at 1000 mg/kg caused significant increases in the incidences of preimplantation loss in females successfully mated and of postimplantation loss in females having implantations. Uterine decidualization in pseudopregnant rats was significantly decreased at 1000 mg/kg. These findings suggest that early embryonic loss due to MBuP is mediated, at least in part, via suppression of uterine decidualization, an impairment of uterine function.

Effects of dibutyl phthalate on reproductive function in pregnant and pseudopregnant rats.

In our previous studies, dibutyl phthalate (DBP) was found to be embryolethal and teratogenic in rats. In this study, the effects of DBP on reproductive function were investigated on pregnant and pseudopregnant rats. Rats were given DBP by gastric intubation at 0, 250, 500, 750, 1000, 1250 or 1500 mg/kg on Days 0 to 8 of pregnancy and the pregnancy outcome was determined on Day 20 of pregnancy. The same doses of DBP were given to pseudopregnant rats, with an induced decidual cell response, on Days 0 to 8 of pseudopregnancy, and the uterine weight on Day 9 served as an index of the uterine decidualization. DBP caused significant increases in the incidences of preimplantation loss in females successfully mated at 1250 and 1500 mg/kg and of postimplantation loss in females having implantations at 750 mg/kg and above. The uterine decidualization in pseudopregnant rats was significantly decreased at 750 mg/kg and above. These findings suggest that early embryonic loss due to DBP may be mediated, at least in part, via the suppression of uterine decidualization, an impairment of uterine function.

Reproductive effects of butyl benzyl phthalate in pregnant and pseudopregnant rats.

In our previous studies, butyl benzyl phthalate (BBP) was found to be embryolethal and teratogenic in rats. In this study, the reproductive effects of BBP were investigated in pregnant and pseudopregnant rats. Rats were given BBP by gastric intubation at 0, 250, 500, 750, or 1000 mg/kg on Days 0 to 8 of pregnancy and the pregnancy outcome was determined on Day 20 of pregnancy. The same doses of BBP were given to pseudopregnant rats, with an induced decidual cell response on Days 0 to 8 of pseudopregnancy, and the uterine weight on Day 9 served as an index of the uterine decidualization. BBP caused significant increases in the incidences of preimplantation loss in females successfully mated at 1000 mg/kg and of postimplantation loss in females having implantations at 750 mg/kg and above. Uterine decidual growth in pseudopregnant rats was significantly decreased at 750 mg/kg and above. These findings suggest that early embryonic loss due to BBP may be mediated, at least in part, via the suppression of uterine decidualization, an impairment of uterine function.

Effects of triphenyltin chloride on implantation and pregnancy in rats.

The objective of this study was to characterize the adverse effects of triphenyltin chloride (TPTCl) during early pregnancy. Following successful mating, female rats were given TPTCl by gastric intubation at 3.1, 4.7, or 6.3 mg/kg on days 0 to 3 of pregnancy or at 6.3, 12.5, or 25.0 mg/kg on days 4 to 6 of pregnancy and were sacrificed on day 20 of pregnancy. In successfully mated females, TPTCl totally prevented implantation in a dose-dependent manner. The pregnancy rate was significantly decreased after administration of TPTCl on days 0 to 3 at 4.7 and 6.3 mg/kg and on days 4 to 6 at 12.5 and 25.0 mg/kg. In females having implantations, the numbers of implantations and live fetuses and the incidences of pre- and postimplantation loss and fetal malformations in the TPTCl-treated groups were comparable to the controls. It could be concluded that TPTCl during early pregnancy causes failure in implantation and TPTCl has greater antiimplantation effects when administered during earlier than later stages of blastogenesis.

Characterization of developmental toxicity of mono-n-benzyl phthalate in rats.

The objective of this study was to characterize the developmental toxicity of mono-n-benzyl phthalate (MBeP), which is one of the major metabolites of n-butyl benzyl phthalate. Pregnant rats were given MBeP by gastric intubation at 250, 375, 500, or 625 mg/kg on days 7 to 9, 10 to 12, or 13 to 15 of pregnancy. A significantly increased incidence of postimplantation loss was found at 500 mg/kg and above regardless of the days of administration. While administration of MBeP on days 7 to 9 or 13 to 15 at 375 mg/kg and above was significantly teratogenic, no evidence of teratogenicity was detected when MBeP was given on days 10 to 12. Deformity of the vertebral column and ribs and dilation of the renal pelvis were frequently observed after administration on days 7 to 9. Cleft palate and fused sternebrae were exclusively found after administration on days 13 to 15. These findings indicate that the susceptibility and spectrum of the developmental toxicity of MBeP vary with the developmental stages at the time of administration.