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Biomedical subjects

E Hirsch

Publications and source records attributed to E Hirsch.

At least 19 recordsLinked to original sources

Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats.

Lithium is known to potentiate the ability of pilocarpine to induce status epilepticus in rats. The goal of this study was to determine whether lithium could potentiate pilocarpine-induced seizures in developing animals. Behavioral, electroencephalographic (EEG), and histopathological changes induced by systemic administration of lithium (3 meq/kg) followed 20 h later by pilocarpine (3, 10, 30, 60 mg/kg) were studied in 3-30-day-old rats. Lithium followed by pilocarpine (30 and 60 mg/kg) induced hyperactivity, tremor, loss of postural control and scratching but no electrographic seizures in 3-8-day-old rats. In the 7-10-day-old animals pretreatment with lithium and pilocarpine 60 mg/kg induced status epilepticus with sustained myoclonus and continuous bilateral synchronous spike and sharp wave, but doses of pilocarpine lower than 60 mg/kg had no effect. The susceptibility to lithium-pilocarpine-induced status epilepticus increased markedly during the third postnatal week of life. During this time period, rats treated with lithium (3 meq/kg) plus pilocarpine 10 mg/kg exhibited behavioral and EEG manifestations of status epilepticus. The same combination of lithium and pilocarpine failed to induce status epilepticus either before or after the third week of life. Histopathological analysis of the brains of the animals used in these studies failed to demonstrate the widespread damage reported in adult rats that have undergone lithium-pilocarpine-induced status epilepticus.

Aging

Dorsal tegmentum kindling in rats.

Electrical stimulations were applied daily for 40 days to the dorsal tegmentum in 9 rats through chronically implanted bipolar electrodes. The intensity of current (2 s trains of 50 Hz, 1 ms monophasic square waves) necessary to trigger a full tonic seizure was determined and applied for all further stimulations. Initial stimulations induced a tonic seizure with a low voltage fast electrocorticographic activity. After repeated stimulations, high amplitude spike and wave discharges developed over the cortex, their duration exceeding 50 s at the 40th stimulation. Simultaneously, the tonic seizures evolved into tonic-clonic fits with bilateral myoclonias following the tonic phase. These EEG and behavioral modifications persisted for 30 days after the last stimulus. These results demonstrate that kindling may be obtained from brainstem structures.

Animals

Corticotropin-releasing hormone-induced seizures in infant rats originate in the amygdala.

The neuroanatomical substrate of seizures induced by picomolar amounts of corticotropin-releasing hormone in infant rats was investigated. Electrographic and behavioral phenomena were monitored in 42 rat pups aged 5 to 22 days. Rat pups carried bipolar electrodes implanted in subcortical limbic structures, as well as cortical electrodes and intracerebroventricular cannulae. The administration of corticotropin-releasing hormone produced age-specific seizures within minutes, which correlated with rhythmic amygdala discharges. Paroxysmal hippocampal and cortical discharges developed subsequently in some rats. Corticotropin-releasing hormone-induced electrographic and behavioral seizures originate in the amygdala.

Aging

Positive transfer of audiogenic kindling to electrical hippocampal kindling in rats.

Audiogenic seizures in genetically susceptible rodents are provoked by intense acoustic stimulations which result in a tonic seizure associated with a short flattening of the EEG. These seizures have been shown to involve primarily brainstem structures. Daily exposure to sound for 30-40 days produced a permanent change in the evoked seizure with development of facial myoclonias, rearing and falling, or of tonic-clonic seizures accompanied by high amplitude cortical spike-and-wave discharges. Kindled audiogenic seizures appear similar to seizures kindled from amygdala or hippocampus, suggesting that repeated auditory stimulations cause a progressive propagation of the epileptic discharge toward limbic structures. To verify this hypothesis, the behavioral and EEG development of electrical hippocampal kindling has been studied in 7 non epileptic controls (NE), 8 acoustic susceptible (AS), and 8 audiogenic kindled rats (KAS). The behavioral and EEG development of the electrical hippocampal kindling was similar in the AS and the NE rats. However, 2 animals in the AS group but no controls exhibited behavioral running and bouncing during the course of hippocampal kindling. In the KAS group, the hippocampal kindling was clearly facilitated as compared to NE and AS: behavioral stage greater than or equal to 5 was reached in a mean of 4 stimulations in KAS versus 30 and 22 stimulations respectively in NE and AS groups. This positive transfer phenomenon suggests that during kindling of audiogenic seizures, epileptic discharge spreads from the brainstem to the forebrain and progressively involves the hippocampus.

Acoustic Stimulation

Section of the corpus callosum in kainic acid induced seizures in rats: behavioral, electroencephalographic and neuropathological study.

Clinical and experimental data suggest that the role of corpus callosum in epilepsy includes synchronization, spread, excitation and inhibition. Section of the corpus callosum (SCC) is known to be a useful therapy in selected types of generalized epilepsy, i.e., tonic, atonic and generalized convulsive seizures, but not partial seizures which may be exacerbated by this procedure. The goal of this study was to determine the effect of SCC in the kainic acid (KA) model of limbic seizures in rats. Using several doses of KA (2.5, 5 and 10 mg/kg) injected systemically, we found a potentiation of the behavioral, electrographic and histological effects of KA in the SCC group of animals compared to the sham-operated control rats. A low dose of kainic acid (2.5 and 5 mg/kg) induced status epilepticus in the SCC animals, but not in the sham-operated control rats. These data demonstrate that in the KA model of temporal lobe seizures, SCC not only fails to protect, but actually intensifies seizures. This finding is compatible with the hypothesis that there is an inhibitory influence, via the corpus callosum, of the non epileptic neocortex on its contralateral homologue in the kainic acid model.

Animals

Corpus callosotomy in the lithium-pilocarpine model of seizures and status epilepticus.

Section of the corpus callosum (SCC) is a useful surgical therapy in selected types of epilepsy, i.e., tonic, atonic, and intractable generalized convulsive seizures. Experimentally, the effects of SCC have been documented in animal models of focal seizures as well as generalized seizures. The object of this study was to determine the effect of SCC on behavioral and EEG symptomatology in the lithium-pilocarpine model of seizures and status epilepticus in the rat. SCC was well tolerated. Fifty-seven percent of SCC animals never developed status epilepticus, while all control animals developed status epilepticus. None of the SCC animals died after 24 h but 59% of control animals died within 24 h of status. Histology verified the extent of the SCC and demonstrated widespread brain damage in all animals who exhibited status epilepticus after 72 h. SCC was associated with a lesion of hippocampal commissure in 64% of animals in the SCC group. This protective effect was not related to lesion of the skull or the longitudinal sinus. The lesion of the hippocampal commissure may have contributed to the protective effect of SCC, since animals with an isolated lesion of the hippocampal commissure without SCC survived the status and showed an increased latency to seizure and status epilepticus. These data suggest that the lithium-pilocarpine model of status epilepticus may be useful in the study of the mechanism of efficacy of SCC in the treatment of epilepsy.

Animals

Student mental health needs: survey results and implications for service.

In preparation for planning counseling and mental health services at Columbia University, the authors conducted a mental health needs assessment survey that sampled representative numbers of students. Respondents were most concerned about academic and school-related issues, followed by concerns in the area of love relationships. Multiple regression analysis revealed certain subgroups that were more likely to have these concerns and certain health and mental health problems that were significantly associated with these concerns. The study identified serious psychological problems, including suicidal/homicidal thoughts and sexual abuse, and surveyed respondents' treatment preferences. Finally, the authors discuss how the study findings contributed to sharpening and expanding focus on different aspects of program development in the collaboration between mental health and health education.

Adult

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

Adolescent

Contralateral disappearance of parkinsonian signs after subthalamic hematoma.

A man with Parkinson's disease (PD) suddenly developed a left hemiballismus, and the CT showed a hematoma of the right subthalamic nucleus. After the ballistic movements had disappeared, akinesia and the other parkinsonian signs did not reappear on the left. This clinical case confirms the involvement of the subthalamic nucleus in the akinesia of PD, as suggested by recent experimental data.

Aged

[Paroxysmal neurological manifestations disclosing panic attacks].

Thirty-seven patients presented with paroxysmal neurological manifestations attributed to anxiety attacks. The manifestations included loss of consciousness, focal sensorimotor deficits, diffuse dysesthaesiae, visual disorders and tremor. They lasted 10 to 45 minutes and occurred once per day to once per week. Organic pathology was dismissed on the basis of normal examinations and atypical course. In all patients questioning revealed symptoms that were those of acute anxiety. The fact that these attacks took place in suggestive (circumstances e.g. in crowds and car driving), and that they could be induced by challenge tests hyperpnoea, infusion of lactate) suggested that these disorders were consecutive to panic attacks.

Adult

Heterotopic pregnancy with discordant ultrasonic appearance of fetal cardiac activity.

In an interesting experiment of nature, we observed the discordant onset of fetal cardiac activity between the two gestations of a heterotopic pregnancy. After initially detecting cardiac activity only in the tubal gestational sac, we later observed cardiac activity in the intrauterine sac 6 days after laparoscopic salpingectomy. This case illustrates the variable onset of cardiac activity. We advise expectant management of the intrauterine pregnancy in a heterotopic gestation when cardiac activity is not detected initially in the intrauterine sac.

Adult

The management of traumatic aortic tear in the multiply-injured patient.

Patients with traumatic aortic tears and severe life-threatening associated injuries require early and expeditious evaluation and treatment in order to improve survival. Diagnostic and treatment priorities, however, are not clearly established in this subset of patients. The purpose of this retrospective analysis was to help identify successful diagnostic and treatment priorities in this group of patients. Between 1979-1989 the medical records of all patients sustaining blunt chest trauma resulting in a traumatic aortic tear were reviewed. There were 11 patients with multiple injuries and this diagnosis was treated at Boston University Medical Center. Five patients had diagnostic peritoneal lavage or an exploratory laparotomy prior to a thoracotomy. Four patients had only a thoracotomy. Two patients in this series had a thoracotomy prior to treatment of suspected intraabdominal injuries. One of these two patients died. Our overall survival rate was 82%. This series suggests that the management sequence in patients with coexistent injuries should include treatment of severe associated injuries prior to treatment of the aortic injury and that initial treatment of traumatic aortic tears is appropriate if there is no evidence of severe life-threatening trauma.

Adult

Quantitative autoradiography of tyrosine hydroxylase immunoreactivity in the rat brain.

Levels of tyrosine hydroxylase (TH) were quantified in discrete areas of unfixed rat brain tissue sections using a rapid and sensitive radioimmunohistochemical method. The immunological reaction with the TH monoclonal antibody was revealed by a 35S-labelled secondary antibody and thus permitted autoradiographic detection of the enzyme. Autoradiograms were generated by apposition of tissue sections to high-sensitivity films or by dipping into autoradiographic emulsion. A detailed analysis of antibody concentration, incubation time, tissue section thickness, and exposure time of the film was undertaken to determine optimal conditions to produce a linear radiolabelling intensity with respect to the amount of antigen. Quantification of the antigen at regional levels was assessed by computer-assisted image analysis. Autoradiographic optical density of radiolabelling in brain areas was converted to enzyme concentrations by interpolation with a constructed TH calibration curve processed in parallel with tissue sections. The specificity of the labelling and the validity and reproducibility of the quantification were investigated. The distribution of TH radiolabelling was comparable to that described using immunofluorescence histochemistry or measuring TH enzymatic activity on homogenates. Using a 35S-labelled antibody, the detection of TH could be performed at the cellular level.

Animals

Neuronal localization of copper-zinc superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer's disease brains.

The distribution of cells containing copper-zinc superoxide dismutase (CuZn SOD) protein and mRNA was studied in hippocampi from normal humans and patients with Alzheimer's disease (AD) by using immunohistochemistry and in situ hybridization. Using antisera against native and denatured CuZn SOD protein, we have determined that immunostaining was intense in pyramidal neurons of the cornu ammonis, in granule cells of the dentate gyrus and very weak in other cells. In the hippocampus of an Alzheimer's patient, successive immunostaining of the same tissue section by antiCuZn SOD and antipaired helical filaments antisera show that both normal and degenerating cells were labeled by the antiCuZn SOD antiserum. Thus, large pyramidal neurons which are susceptible to degenerative processes in AD have the property to contain high amount of CuZn SOD protein. In situ hybridization was performed on paraformaldehyde-fixed hippocampus sections of normal human brains and AD brains with a 35 S labeled DNA probe homologous to human CuZn SOD mRNA. Our results show that CuZn SOD transcripts are present at high abundance in pyramidal neurons of the CA1-CA4 fields, subiculum, and in granule cells of the dentate gyrus. This cellular distribution is similar to that obtained with the antiCuZn SOD antiserum. This might indicate that biochemical pathways leading to superoxide radicals generation are specially active in these neurons, requiring an active transcription of CuZn-SOD gene.

Aged

[Recurrent aseptic meningitis in periodic disease or Mollaret's meningitis?].

A 33 year-old Sephardic Jewish man with familial mediterranean fever (FMF), presented during a 7 year period, 6 episodes of aseptic meningitis, improving within less than 24 h after spinal tap. Cerebrospinal fluid analysis showed a mixed leucocytic pleocytosis ranging from 100 to 1,000 cell/mm3. Spinal fluid cultures for bacteria, viruses and viral antibodies were always negative. Our case supports other reports showing that recurrent aseptic meningitis, although rare, may occur in FMF. It usually responds to treatment with colchicine, like other manifestations of the disease. FMF meningitis has been compared to Mollaret's meningitis whose cause is undetermined. However, Mollaret's meningitis, unlike FMF, is sporadic and ubiquitous, is not transmitted genetically and affects men and women equally. Moreover, in Mollaret's meningitis transient neurological abnormalities, such as signs of encephalitis have often been reported: polyserositis or associated amylosis are absent, there is no biological inflammatory syndrome, and in 65% of the patients the CSF contains specific large mononuclear-derived cells called endothelial cells. Such abnormalities have not been described in FMF.

Adult

[Postures and abnormal paroxysmal movements during sleep: hypnogenic paroxysmal dystonia or partial epilepsy?].

In recent years, a differentiation has been made between two syndromes that are characterized by brief abnormal paroxysmal movements occurring principally at night: 1, hypnogenic paroxysmal dystonia (HPD), sometimes considered a particular form of dystonia similar to paroxysmal kinesigenic choreoathetosis, and 2, mesiofrontal epilepsy. Whether HPD is a distinct syndrome is not clear. Twenty-three patients, 11 men and 12 women, were hospitalized between 1985 and 1989 for examination of this type of abnormal paroxysmal movements (APM) occurring at night. In order to clarify the physiopathology of these abnormal nocturnal movement as focal epilepsy or a particular form of dystonia, we analyzed the personal and familial antecedents of all 23 patients, the polygraphic records during waking and sleep periods, and the results of neuroradiological examinations. Four patients were examined by positron emission tomography (PET) using i8F deoxyglucose. Symptoms first appeared between 3 and 28 years of age (M, 10.1) and developed over 1 to 20 years (M, 10.1). APM clearly occurred more commonly (greater than 90%) during sleep, usually during phases of slow-wave sleep. The sleeping patient opened his eyes and the motor signs then variously associated affective facial expression; axial postural modifications; tonic, dystonic or choreic postural movements of the limbs; pedalling; automatisms; disordered agitation and vocalization. The seizure was abruptly interrupted after 10 to 60 seconds. There was usually no postictal confusion. Thirteen patients clearly had clear epileptic antecedents: in 9, generalized tonic-clonic seizures; in 4, focal epileptic status. During nocturnal polygraphic recording, 6 patients presented a generalized seizure following a period of APM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Diagnostic of precipitant for biomacromolecule crystallization by quasi-elastic light-scattering.

The translational diffusion coefficient D25,w of hen egg-white lysozyme and concanavalin A from the jack bean is measured in various precipitating agent solutions as a function of salt and protein concentration using quasi-elastic light-scattering. With some precipitants, in undersaturated protein solutions, a protein or salt concentration dependence of the diffusion coefficient of the scatters is observed. It can be correlated with the inability of the protein to crystallize in this precipitant once the solution is supersaturated. These variations of D25,w are interpreted in terms of non-specific interactions and/or aggregation that prevent the protein from making appropriate contacts to form a crystal. With other precipitants known to lead to crystallization, no significant variation of the diffusion coefficient with increasing concentration was observed, indicating that under such conditions up to saturation the proteins remain essentially monodisperse. Application of this technique to find crystallization conditions of other proteins is discussed.

Ammonium Sulfate