Field and vegetable crop mutants with increased resistance to herbicides.

Wheat mutants with increased seedling resistance to terbutryn (2-tertbutylamino-4-ethylamino-6-methylthio-s-triazine) and tomato mutants with increased resistance to diphenamid (N,N-dimethyl-2,2-diphenylacetamide) were selected by the experimenters out of populations grown from seeds treated with ethyl methanesulfonate. Induced mutations may thus provide a tool for breeding crop cultivars with increased resistance to certain herbicides.

Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results.

BACKGROUND: Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. METHODS AND RESULTS: A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93+/-1% of the lysed clot became subcapillary in size (<8 microm). In vitro safety studies, however, showed arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300 seconds. CONCLUSIONS: External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of

Autosplenectomy complicating pneumococcal meningitis in an adult.

We present a rare complication of pneumococcal meningitis. A 56-year-old female patient with pneumococcal meningitis developed acute hyposplenism. Left-sided hypochondriacal pain accompanied by a marked thrombocytosis developed during the convalescent period. Abdominal radionuclide and computed tomographic scans demonstrated damage to the spleen. The findings were compatible with autosplenectomy.

Calmodulin-binding peptides interfere with melanocyte-stimulating hormone receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R mouse melanoma cells.

The MSH receptor belongs to a unique class of G-protein-coupled receptors, in which calcium ions control the binding affinity of MSH by a yet unknown mechanism. Possible involvement of a calcium-binding protein [e.g. calmodulin (CaM)] in the regulation of MSH receptor activity has been studied in the M2R mouse melanoma cell line. In this study, we tested the inhibitory effects of a group of calmodulin-binding peptides (CBPs) on MSH receptor activities in intact M2R cells and membrane preparations derived from them. We also report here on stimulatory effects of CBPs on cAMP production in M2R cells that could not be produced in other cell lines lacking MSH receptors. This group of CBPs includes synthetic peptides comprising the CaM-binding domains of Ca2+/CaM-dependent enzymes, cytotoxic venom peptides, and peptide hormones that have been reported to directly interact with CaM. The results show that CBPs, at micromolar concentrations, inhibit MSH binding and consequent adenylate cyclase stimulation in a specific and concentration-dependent manner, but have no effect on adenylate cyclase stimulation by prostaglandin E1. On the other hand, when MSH was omitted and forskolin (0.5-1 microM) was added instead, CBPs had the opposite effect on cAMP production, stimulating it in M2R cells, but not in other cell types tested. Thus, these peptides can be considered as antagonists of MSH receptor and partial agonists of M2R adenylate cyclase. In contrast to MSH, the stimulatory effects of CBPs were unaffected by EGTA, suggesting a Ca(2+)-independent action of these peptides. Using phospholipid vesicles and M2R cells, we recently showed that CBP activity in M2R cells may include direct partition into the lipid bilayer of the cell membrane, permitting interaction with hydrophobic lipid-inserted domains of components of the signal transducing machinery. Based on these findings, we suggest that the mechanism of action of CBPs in the M2R cells includes two major components: 1) interaction with the cell surface membrane and penetration into the lipid milieu, and 2) interaction with exposed or lipid-embedded protein epitopes intrinsically associated with the MSH-receptor system, thereby affecting the MSH receptor cascade.

Early treatment of a single generalized tonic-clonic seizure to prevent recurrence.

BACKGROUND: The question of whether to start antiepileptic treatment after a single unprovoked seizure remains controversial and has been the subject of much debate in the relevant literature. OBJECTIVES: To determine the rate of recurrence of a second attack after a single unprovoked epileptic seizure by using 2 study groups of treated and untreated patients and, thus, to establish a treatment policy for these patients. PATIENTS AND METHODS: A group of 91 patients with a single generalized tonic-clonic seizure were prospectively studied; 87 of these patients completed the study. The end point of the study was 36 months after the single attack or the occurrence of a subsequent epileptic attack. The patients were randomly divided into 2 groups; 45 patients who immediately received anticonvulsive treatment and 42 who remained untreated for the follow-up period. Patients in the treated group were given monotherapy with carbamazepine. The results of recurrences were statistically analyzed by using the Kaplan-Meier method. RESULTS: Results indicated a significantly higher percentage of seizure-free patients in the treated group compared with that in the untreated group (P = .001). The treated men were proved to be less at risk for recurrent seizures compared with treated women (P < .001 vs P = .03, respectively). CONCLUSION: Treatment after a single unprovoked seizure leads to a significant reduction in the risk of relapse of generalized tonic-clonic epilepsy.

Selective acalculia with sparing of the subtraction process in a patient with left parietotemporal hemorrhage.

We describe a patient with left parietotemporal hemorrhage with selective acalculia for addition, multiplication, and division, but with an intact ability to subtract. There was no impairment in the ability to distinguish mathematical signs. This case suggests that different processing systems are responsible for each of the basic arithmetic operations.

Anterior operculum syndrome localized by SPECT.

UNLABELLED: The aim of this case report was to present a patient with complete anarthria and orofacial apraxia without other relevant neurological deficit. The clinical features are compatible with anterior operculum syndrome. METHODS: A regional brain perfusion scan was done using 99mTc-HMPAO and a SPECT gamma camera. A brain CT scan and an MRI were also performed. RESULTS: Brain CT and MRI were not diagnostic. On brain SPECT, hypoperfusion of the left inferior area of the frontal lobe was noted. CONCLUSION: The patient studied showed an uncommon case of anterior operculum syndrome of focal degenerative origin localized by SPECT. SPECT may be a useful and effective method for diagnosis of this unusual neurological deficit.

Mydriasis induced by tetrahydrocannabinol (THC) in rats.

Male albino rats, injected intravenously or intracerebroventricularly with delta 1-tetrahydrocannabinol (THC), develop mudriasis. The median effective dose of the intravenous administration group was 5 mg/kg THC, whereas that for the intracerebroventricular route was 150 microgram/kg THC. Sympathectomy significantly decreased the THC-induced mydriasis. The mydriatic effect was not influenced by naloxone. We conclude that THC produces mydriasis through a central action, the efferent pathway of which is the sympathetic system.

Serum dopamine beta-hydroxylase activity in acute cardiac disease.

The activity of dopamine beta-hydroxylase in the serum was measured in patients with acute cardiac disorders who were admitted to a coronary care unit. The activity of the enzyme on admission was similar in patients with acute myocardial infarction and in those with other conditions; on discharge, the activity was reduced significantly. Patients with myocardial infarction had the greatest fall in the activity of dopamine beta-hydroxylase. Patients with multiple signs of sympathetic hyperactivity had significantly higher values for the activity of dopamine beta-hydroxylase on admission. Pain was found to significantly increase the activity of the enzyme. These data confirm findings that the activity of dopamine beta-hydroxylase in the serum reflects the intensity of sympathetic activity. The factors contributing to the elevated sympathetic activity in some patients with acute myocardial infarction seem to be nonspecific, but because of the ominous nature of increased sympathetic tone in this condition, it could be advantageous to identify these patients.

Signaling mechanisms controlled by melanocortins in melanoma, lacrimal, and brain astroglial cells.

Melanocortins appear to be involved as regulators in an ever growing number of physiological processes in cells and tissues of diverse functions. While such trends are apparent also in the case of other peptide hormones, it appears that melanocortin receptors can be regarded as unique among G-protein-linked receptors due to their special need for extracellular Ca2+ which may relate to some, yet undetermined selectivity of their actions. The physiological role that Ca2+ may be playing and the diverse signaling mechanisms regulated, as well as the nature of the cell-specific responses elicited in melanocortin-sensitive cells/tissues, have yet to be elucidated. Likewise, it will be of interest to establish the relationship of melanocortins to processes like growth and differentiation of cells, as well as to higher, more complex processes such as those regulated in the CNS.

Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke.

Magnesium has been reported to have a dilatatory effect on cerebral arteries. Reduction of extracellular Mg+2 has been shown to be directly correlated with the intensity of cerebral spasm. A neuroprotective effect of magnesium in stroke has also been hypothesized. The aim of our study was to examine the Mg+2 levels in serum and cerebrospinal fluid (CSF) in the early stage of stroke and to evaluate the correlation between Mg+2 levels and the development of neurological deficits. Between 1986 and 1994, 96 patients who had a stroke of 24- to 48-h duration were enrolled in the study. Serum and CSF levels of magnesium were checked on admission, 2448 h after the onset of stroke. Using a neurological score, the neurological deficit was assessed on the 1st day, 1 and 4 weeks later. Computed tomography (CT) was performed after 1 week, and the volume and location of infarction were calculated and measured. Statistical analysis was performed for cortical and subcortical patients separately, using Spearman correlation and multiple linear and logistic regression analyses. Significant correlation was found between CSF Mg+2 and the size of the infarct (P < 0.0001). There was no correlation between serum Mg+2 and CSF Mg+2 levels. Regression analysis demonstrated an increase in the values of the Mathew Neurological Score with higher CSF Mg+2 levels. This association remained true after other factors such as age, associated heart disease, diabetes and infarction size had been taken into account by the regression model. The results confirm that there is a relationship between a low Mg+2 concentration in CSF during the first 48 h after onset of ischaemic stroke and the intensity of the neurological deficit. The therapeutic consequence of this finding may have some importance.

Enkephalin mydriasis in mice.

Morphine is known to produce mydriasis in mice. We have found that enkephalins caused a similar effect. Morphine was twice as active as D-Ala-D-Leu-enkephalin (BW-180C), 5 times as active as Met-enkephalin and 7 times as active as Leu-enkephalin. The time course of the effect was shortest for the enkephalins ( t 1/2 = 8-12 min), intermediate for BW-180C (60 min) and longest for morphine (80 min). Naloxone antagonised the effect of all agents to a similar extent. The question whether enkephalins are involved in the physiological regulation of pupillary diameter was investigated by administering either naloxone or D-phenylalanine to mice. None of these agents changed pupillary size, thus making such an involvement unlikely.

The stability of dopamine-beta-hydroxylase activity in blood samples.

Dopamine-beta-hydroxylase activity was measured in serum samples that were incubated at 37 degrees C for up to seven days and were compared with preincubation values. No change of activity was observed.

Somatostatin mydriasis in mice.

Administration of somatostatin intracerebroventricularly to mice produced a dose-dependent mydriasis, whereas intravenous injections were ineffective. Naloxone could prevent or abolish this effect. It is suggested that somatostatin either directly excites opiate receptors or activates endopioid pathways involved in the regulation of pupillary size.

Weight gain, increased appetite, and excessive food intake induced by carbamazepine.

Four young patients who developed weight gain induced by carbamazepine therapy are described. The patients received the carbamazepine as anticonvulsant treatment, and soon after starting the drug, abruptly developed an increase in appetite with a concomitant increase in food intake. During a period of 2 months the patients' weights rose by between 7 and 15 kg. Dietary restriction during the carbamazepine treatment was ineffective in promoting weight loss, and loss of the excess weight was achieved only when the drug was discontinued. These patients demonstrate an as yet unpublished adverse effect of carbamazepine. In carbamazepine-induced weight gain, overeating and fat deposition must be taken into consideration as a differential diagnosis to the hitherto described water retention and edema.

Intravenous administration of magnesium sulfate in acute stroke: a randomized double-blind study.

A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001) and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/- 1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.

Correlation between skull thickness asymmetry and scalp potential estimated by a numerical model of the head.

The contribution of asymmetric skull thickness to the scalp potential amplitude was investigated numerically. The model consisted of four conductive layers representing the scalp, the skull, the cerebrospinal fluid, and the cortex with a current dipole in the occipital region. The potential created by the dipole was calculated assuming quasistatic formulation and linear media. The governing equation was discretized by the finite volume method to ensure the conservation of fluxes even in regions with abrupt changes of the conductivity. The large set of the algebraic equations for the electric potential was solved iteratively by the successive overrelaxation method. The model confirmed previous experimental studies suggesting that the potential amplitude is 60% smaller on the side with the thicker bone if the asymmetry of the skull thickness exceeds 40%. The model developed suggests that skull thickness asymmetry can create nonnegligible asymmetries in the potential measured on the scalp above homotopic points of the two hemispheres.

Familial dyslexia associated with cavum vergae.

Three members of one family, diagnosed as dyslexic, are described. All of them have variations of midline cavity: cavum vergae or cavum septum pellucidum, diagnosed by neuroradiological examination. In contrast, the non dyslexic members of the same family have no neuroanatomical congenital variations. We raise the possibility of a functional correlation between the dyslexia and the anatomical findings in the affected members of this family.

Strokes mimicking peripheral nerve lesions.

Sensory-motor deficit in a peripheral nerve pattern due to brain lesion is rarely documented. We report on seven patients with a clinical manifestation of sensory-motor deficit, imitating peripheral nerve involvement, due to lacunar brain infarcts verified by brain computed tomography scan. Five of the patients had an ulnar nerve-like deficit and two median nerve-like deficits. The infarcts were located in the thalamus and the corona radiata. No clinical or electrophysiological evidence for peripheral nerve involvement was found. The unusual peripheral nerve pattern of lesions caused by lacunar brain infarcts can be defined as an additional lacunar syndrome and must be taken into consideration in the clinical evaluation of peripheral nerve deficits with normal nerve conduction velocity.

Splinting therapy for congenital auricular deformities with the use of soft material.

Congenital auricular deformities present serious esthetic problems. To avoid surgical correction, splinting during the early neonatal period has been attempted. We describe the results and follow-up of splinting therapy with a special soft material in 30 neonates, as compared with results in a control group of 20 untreated newborn infants. Good results were achieved in 85% of the patients and sufficient results in 15% when the treatment was continuous over the entire 4-week period. However, when treatment was partial or discontinuous, only 10% had good results. None of the infants in the control group showed spontaneous improvement during the period of study. Moreover, early initiation of treatment (first week of life) proved more effective than later treatment (second week of life). Strong parental cooperation and close follow-up are also important for success.