Directional limits on persistent gravitational waves using LIGO S5 science data.

The gravitational-wave (GW) sky may include nearby pointlike sources as well as stochastic backgrounds. We perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. Finding no evidence to support the detection of GWs, we present 90% confidence level (C.L.) upper-limit maps of GW strain power with typical values between 2-20×10(-50) strain(2) Hz(-1) and 5-35×10(-49) strain(2) Hz(-1) sr(-1) for pointlike and extended sources, respectively. The latter result is the first of its kind. We also set 90% C.L. limits on the narrow-band root-mean-square GW strain from interesting targets including Sco X-1, SN 1987A and the Galactic center as low as ≈7×10(-25) in the most sensitive frequency range near 160 Hz.

Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

The calcium antagonist properties of cyproheptadine: implications for antimigraine action.

Cyproheptadine is equipotent (IC50 = 41 to 45 nM) in blocking contractions of canine basilar artery segments induced by serotonin, norepinephrine, potassium, or calcium. Methysergide and amitriptyline display variable potencies in inhibiting contractions depending on the initiating agent. Propranolol, at concentrations to 10 micromolar, had minimal effect on vessel contractions. We conclude that the primary action of cyproheptadine in preventing induced contractions of the canine basilar artery is antagonism of calcium channels. This action is unique among drugs used for migraine prophylaxis and may have important implications for the treatment of headache and other neurologic disorders.

Role of calcium antagonists in cerebral arterial spasm.

Spasm of the large cerebral arteries at the base of the brain causes delayed ischemic neurologic deficits in approximately 30% of patients after a subarachnoid hemorrhage from an intracranial aneurysm. In vitro chamber studies have shown that both dog and human large cerebral artery segments contract to a variety of vasoactive agents, and the dog and human segments are remarkedly similar in their responses. The source of calcium necessary to initiate contraction was found to be extracellular for large cerebral arteries. In contrast, systemic arteries such as the femoral artery use a bound intracellular pool of calcium for contraction. The calcium antagonists nifedipine and nimodipine were found to selectively inhibit the contractions of large cerebral arteries but not the femoral artery. In vivo experiments demonstrated that both nifedipine and nimodipine, given sublingually, would prevent and reverse cerebral arterial spasm in the dog after a subarachnoid hemorrhage. Nimodipine was found to be more potent, both in the chamber and in the live dog experiments. Nimodipine significantly decreased the occurrence of severe neurologic deficits from spasm alone in a multi-institutional, prospective, double-blind, randomized, placebo-controlled trial.

Effects of the muscarinic agonist McN-A-343 on the release by sympathetic nerve stimulation of (3H)-noradrenaline from rabbit isolated ear arteries and guinea-pig atria.

1 McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride) in concentrations of 10(-5) and 10(-4)M inhibits the stimulation-induced efflux of radioactivity from segments of rabbit ear artery that have previously been incubated with (-)-[(3)H]-noradrenaline, and also decreases the contractile response.2 The inhibitory effects of McN-A-343 (10(-5)M) on the efflux of radioactivity and the contractions induced by low frequencies of stimulation (2 and 5 Hz) are reversed by atropine, but atropine does not modify these effects with high frequencies of stimulation (20 and 50 Hz).3 McN-A-343 (10(-4)M) enhances the stimulation-induced efflux of radioactivity from guinea-pig atria that have previously been incubated with (-)-[(3)H]-noradrenaline, and prolongs the positive inotropic response. These effects are not modified by atropine.4 It is concluded that McN-A-343 has different effects on adrenergic transmitter release in the two tissues. In the artery, it acts as an agonist on muscarinic receptors of adrenergic terminals to inhibit transmitter release at low frequencies of stimulation. In the atria it enhances transmitter efflux from the tissue, largely by inhibiting re-uptake.

Effects of McN-A-343 and DMPP on the uptake and release of 3 H-noradrenaline by guinea-pig atria.

1. McN-A-343 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride and DMPP (N,N-dimethyl-N'-phenylpiperazinium iodide) inhibit the uptake of (+/-)-(3)H-noradrenaline by guinea-pig atria, being approximately as potent as cocaine in this respect.2. The inhibition of uptake produced by McN-A-343 or DMPP was not affected by atropine or hexamethonium in concentrations which antagonized actions on muscarinic and nicotinic receptors respectively.3. McN-A-343 in the presence of atropine had a positive inotropic action on atria, but this was not accompanied by efflux of radioactivity from atria previously incubated with (-)-(3)H-noradrenaline.4. In the presence of McN-A-343, responses of atria to noradrenaline were increased and those to tyramine were decreased.5. DMPP had positive inotropic and chronotropic actions on atria, and these effects were accompanied by an increase in efflux of radioactivity from atria previously incubated with (-)-(3)H-noradrenaline.

Comparison of effects of six cholinomimetic drugs on inhibition of uptake of 3 H-( )-noradrenaline by guinea-pig atria.

The effects of N,N-dimethyl-N'-phenyl-piperazinium (DMPP), 4-(m-chlorophenyl-carbamoyloxy) - 2 - butynyltrimethylammonium chloride (McN-A-343), pilocarpine, acetylcholine, methacholi-ne and nicotine in inhibiting the uptake of (3)H-(+/-)-noradrenaline by guinea-pig atria were compared. In concentrations of 1 x 10(-4)M, the percentage inhibitions were as follows: DMPP, 89.1%; McN-A-343, 78.7%; pilocarpine 43.5%; acetylcholine, 35.7%; methacholine, 32.9%; nicotine, 21.6%.

Modulation by acetylcholine of adrenergic transmission in the rabbit ear artery.

1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission.

Traumatic lung herniation.

Traumatic lung herniation is a poorly described entity. An important factor in the etiology of these lesions is the relative lack of muscular support afforded by the anterior thorax. We report a case of blunt thoracic trauma complicated by an incarcerated lung herniation.

Neonatal striatal grafts prevent lethal syndrome produced by bilateral intrastriatal injection of kainic acid.

It is reported that unilateral grafts of neonatal striatal tissue protect the recipient from the lethal aphagia and adipsia produced by bilateral intrastriatal injection of 10 nmol of kainic acid in rats. It is shown that neither adult striatum nor neonatal tissue from other sites have the same lifesaving effect and that the salutary effect of the graft is dependent upon graft survival. Grafts from a histoincompatible donor are apparently rejected, leading to the death of the recipient. Cyclosporine inhibits rejection thereby enabling recipient survival. It is postulated that the graft exerts a neurohumoral influence that protects the striatum from the toxic effect of kainate.

Serotonin-induced contraction of canine basilar artery: mediation by 5-HT1 receptors.

Serotonin and related agonists cause a marked contraction of canine basilar artery segments. These contractions can be inhibited by a variety of serotonergic antagonists. Absolute potencies of both serotonin agonists and antagonists in chamber contraction studies significantly correlate (P less than 0.01) with their potencies for 5-HT1, but not 5-HT2, receptors as defined by central nervous system radioligand binding studies. Serotonin-induced contractions of canine basilar artery segments appear to be mediated by 5-HT1 receptors.

Pulmonary contusion: are children different?

BACKGROUND: Pulmonary contusion (PC) is a common sequelae of blunt trauma in adults and children; previous reports suggest that children have more favorable outcomes because of differences in mechanisms of injury, associated injury, and physiologic response. Our objective was to determine whether children who sustain PC have different outcomes compared with similarly injured adults. STUDY DESIGN: Our Level I Trauma Registry was reviewed for a 4-year period and identified 251 consecutive patients who sustained PC. Their charts were reviewed retrospectively for demographics, injury mechanism, injury severity scores, associated injuries, and outcomes (measured by the need for intubation, ventilation days, pneumonia, acute respiratory distress syndrome, and death). Data are expressed as the mean +/- SEM. The Student's t-test was used to compare the groups. A p value less than 0.05 was considered significant. RESULTS: Of the study patients, 41 (16%) were children (ages 2-16, mean 10 years) and 210 (84%) were adults (ages 17-80, mean 34 years). The most common injury mechanisms in children were motor vehicle accidents (56%) and auto-pedestrian accidents (39%), but in adults, motor vehicle accidents (80%, p = 0.02) predominated. Injury severity score was not significantly different between groups (children, 26 +/- 2 and adults 25 +/- 1). Similarly, the incidence of associated injuries was not different between children and adults: head 78% versus 62%, abdomen 59% versus 43%, and skeletal fractures 41% versus 29%, respectively. Neither need for intubation, ventilator days, pneumonia, acute respiratory distress syndrome, or death differed significantly between groups. CONCLUSIONS: Although children and adults differ in regard to injury mechanism, their overall injury severity, associated injuries, and outcomes are quite similar. Thus, contrary to previous reports, children do not have a more favorable outcome after PC.

Delayed diagnosis of blunt duodenal injury: an avoidable complication.

BACKGROUND: There is controversy about the impact on morbidity from delayed diagnoses of blunt hollow viscus injuries. A recent study suggested that the increased morbidity was primarily from delayed diagnosis of blunt duodenal injury (BDI). STUDY DESIGN: We studied the medical records from a 10-year period from June 1987 to June 1997 examining the data on 22,163 cases of blunt trauma. We assessed the incidence and consequences of delayed diagnoses of BDI, and identified preoperative factors associated with these delayed diagnoses. RESULTS: Thirty-five patients (0.2%) were identified in the retrospective study of the records from 22,163 blunt trauma patients to have sustained BDI. Of these, 25 patients (71%) were male. Ages ranged from 1 to 58 years (mean 18.8 years), and the predominant mechanism was motor vehicle accident in 18 patients (51%). Seven patients (20%) (group I) had a diagnostic delay of > 6 hours; 28 patients (80%) (group II) were diagnosed in < 6 hours. Six of the seven group I patients (86%) were evaluated initially with CT scans, and five (83%) showed findings suggestive of BDI. Among the 28 group II patients, 14 (50%) underwent initial diagnostic peritoneal lavage (DPL), and 14 (50%) had a CT scan. In seven of the group II patients (50%) who were initially evaluated by CT scan, there were findings suggestive of BDI. Diagnostic peritoneal lavage was initially equivocal (red blood cell count=5,000 to 100,000) in the remaining one group I patient compared with three of the group II patients who had DPL. Deterioration found on physical examinations prompted followup CT scans in 6 group I patients (86%), and the scans were diagnostic for BDI in all cases. CONCLUSIONS: Blunt duodenal injury is an uncommon entity. Despite the presence of suggestive CT and DPL findings, the diagnosis was delayed in 20% of the 35 patients whose records were examined in the study; this delayed diagnosis was associated with increased abdominal complications. Patients with persistent abdominal complaints and equivocal CT or DPL findings should undergo laparotomy or repeat CT scan evaluations.

Alteration of kainic acid and quinolinic acid toxicity by neostriatal transplants in vitro.

Mature (greater than 21 days in vitro) organotypic corticostriatal cultures prepared from newborn rat brain were incubated in either kainic acid (KA) 10(-3) M or quinolinic acid (QUIN) 10(-3) M for up to 48 h. Other identical cultures were similarly incubated immediately after they had received one or two additional explants of neonatal striatal tissue placed beside each corticostriatal culture. The cultures incubated with either KA or QUIN in the presence of the neonatal striatal tissue showed better preservation than cultures incubated with KA or QUIN alone. Results suggest that the neonatal striatal explants or 'transplants' afford some protective effect against the toxicity or either KA or QUIN.

Occluded but nonthrombosed internal carotid artery: an indication for endarterectomy.

The indications for carotid endarterectomy are sometimes imprecise. Total occlusion of the internal carotid artery has often implied irreversibility. Carotid thromboendarterectomy was performed on eight patients who on angiography had a complete occlusion of proximal internal carotid artery but showed antegrade opacification of the infraophthalmic carotid siphon. Direct magnification, delayed radiography, and subtraction were used on all patients. In five of eight patients, normal antegrade cervical internal carotid blood flow was restored. The possible restoration of the occluded internal carotid artery lumen offers a viable alternative to bypass surgery in selected cases.

Cerebral arterial spasm: A discussion of present and future research.

The author presents a discussion of research on cerebral arterial spasm. Arterial smooth muscle contraction, receptor and relaxation mechanisms are presented in the context of what is known about cerebral arterial spasm and the biochemistry of vascular smooth muscle. Several new experimental approaches are suggested and a theoretical biochemical basis for the idea that damage to the artery alone could cause cerebral arterial spasm is postulated. Methods of determining cerebral arterial spasm and the need for a quantitative, in vivo method are discussed and the question of an irreversible stage of cerebral arterial spasm is considered. Finally, the problems associated with the delivery of a potentially successful treatment to the cerebral arterial smooth muscle cells are examined.

Cerebral arterial spasm: part 9. In vitro effects of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries.

We performed in vitro experiments with a small volume chamber to determine the inhibitory effect of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries. Nifedipine, an inhibitor of the influx of extracellular calcium into smooth muscle cells, was found to be a sensitive inhibitor of contractions of the basilar artery induced by all three agents. In contrast, nifedipine did not significantly inhibit the serotonin- and phenylephrine-induced contractions of the femoral artery but did inhibit potassium-induced contractions of the femoral artery. Calcium-induced contractions of the basilar artery were also inhibited by nifedipine. These experiments demonstrate a relatively selective effect of nifedipine on the basilar artery, and a mechanism to explain this selective effect is postulated.

Cerebral arterial spasm: part 10. Reversal of acute and chronic spasm in dogs with orally administered nifedipine.

In vivo experiments in dogs demonstrated angiographically that the subarachnoid injection of blood produced cerebral arterial apasm both immediately after the injection of blood and 2 days later. The sublingual adminstration of nifedipine reversed both the acute and the delayed cerebral arterial spasm. In addition, sublingual administration of nifedipine 20 minutes before the subarachnoid injection of blood prevented the acute spasm.

Pituitary transplantation: cyclosporine enables transplantation across a minor histocompatibility barrier.

Pituitary glands from neonatal donors were transplanted to the median eminence of hypophysectomized adult rats. Rats with transplants were then treated for 2 weeks with the immunosuppressive drug cyclosporine. For 5 weeks thereafter, blood was drawn at regular intervals for determination of serum thyroxine, prolactin, and luteinizing hormone. Cyclosporine-treated recipients of grafts with minor histocompatibility differences had normal levels of thyroxine and prolactin, whereas untreated animals did not. In addition, the treated animals responded to oophorectomy with a marked elevation in serum luteinizing hormone. This evidence indicates that cyclosporine enables successful transplantation across a minor histocompatibility barrier. It also suggests that these grafts interact with the hypothalamus. Transplantation across a major histocompatibility barrier was unsuccessful even in the presence of cyclosporine.

Microsurgical endarterectomy of the intracranial vertebral artery for vertebrobasilar transient ischemic attacks.

Two patients who had typical vertebrobasilar transient ischemic attacks (TIAs) that were refractory to anticoagulation with dicumarol and to antiplatelet therapy with aspirin and/or dipyridamole are described. Angiography revealed in both patients a stenotic atherosclerotic plaque of the intracranial vertebral artery between the posterior and anterior inferior cerebellar arteries. At operation, the first patient had an atherosclerotic plaque extending into the basilar artery, and no endarterectomy was attempted. The second patient had a 1-cm localized plaque that was removed successfully from the vertebral artery. Neither patient sustained a neurological deficit as a result of the operation. The patient whose plaque was not removed at operation continues to have vertebrobasilar TIAs and suffered a brain stroke 2 weeks after operation. The patient whose plaque was removed at operation continues to be free of TIAs 8 months later, and angiography performed 3 months after operation showed a widely patent vertebral artery. A portion of the intracranial vertebral artery has now been shown to be accessible to endarterectomy using the operating microscope. Angiography is helpful in determining this accessibility preoperatively.