Selective alleviation of compulsive lever-pressing in rats by D1, but not D2, blockade: possible implications for the involvement of D1 receptors in obsessive-compulsive disorder.

Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward. This behavior may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder. In the present study, we tested the hypothesis that the compulsive behavior induced by signal attenuation is mediated via D(1) rather than D(2) receptors. Administration of 0.005, 0.01 and 0.03 mg/kg of the D(1) antagonist SCH 23390 reduced the number of compulsive lever-presses without affecting the number of lever-presses followed by an attempt to collect a reward. In contrast, administration of 0.005, 0.01, 0.024, 0.036 and 0.05 of the D(2) antagonist haloperidol dose-dependently decreased both types of lever-presses. In addition, haloperidol at doses that decreased lever-pressing in the post-training signal attenuation procedure (0.036 and 0.05 mg/kg) had a similar effect in regular extinction, whereas an SCH 23390 dose that decreased compulsive lever-pressing in the post-training signal attenuation procedure (0.01 mg/kg) had no effect on regular extinction. On the basis of electrophysiological data on the response of dopamine neurons to the omission of an expected reward, these results were interpreted as suggesting that compulsive lever-pressing depends on a phasic decrease in the stimulation of D(1) receptors. The implications of these results for the pathophysiology and treatment of obsessive-compulsive disorder are discussed.     

Characteristics of children and their families at entry into foster care

This study provides an overview of children, their families, and their circumstances at the time that the child entered foster care in Israel. Data regarding a representative sample of 800 children were collected as part of the ongoing operation of a clinical information system set up for Israel's foster care service in 1988. Implications of our findings for interventions are discussed.     

Intravenous magnesium sulphate effect on maternal serum and amniotic fluid cytokines levels in preterm labour patients.

Our objective was to evaluate the effect of intravenous magnesium sulphate administration to patients with preterm labour on maternal serum and amniotic fluid IL-1beta, IL-6, IL-10 and TNFalpha concentrations. Thirty-six patients at 24-34 weeks of singleton gestation, who presented with contractions (> or = 8 in 60 min) had amniocentesis to rule out intrauterine infection. The patients received intravenous MgSO4 for tocolysis. Twenty-six patients had amniocentesis performed before initiation of MgSO4 (controls) while 10 others had the procedure during tocolytic therapy (study patients). Magnesium, IL-1beta, IL-6, TNFalpha and IL-10 concentrations were measured. Study and control groups were statistically compared using Student t test. Mean magnesium levels were significantly higher in the study group (P < 0.01). There were no significant differences between the cytokines levels in maternal serum and in amniotic fluid between the groups. Our results suggest that the mechanism of magnesium as a tocolytic agent may not be mediated via the examined cytokines.     

Ambulatory Mental Health Treatment under Universal Coverage: Policy Insights from Israel

Untested assumptions concerning ambulatory treatment have shaped mental health policies for decades. Three opinions prevail: (1) all use is alike; (2) any use leads to high use; and (3) all high use is discretionary and therefore excessive. These assumptions were tested, using data from a nationwide survey of ambulatory utilizers in Israel, a country that has universal coverage. The findings, based on detailed clinical and treatment records, challenge all three assumptions. Moreover, they document a diversity of clinical needs while also verifying substantial variations in the type, frequency, and duration of treatment provided to meet those needs. In brief, Israeli data do not confirm continuing concerns by policy makers about uncontrollable use of services with expanded mental health coverage. Special policy limitations on mental health treatment should be reconsidered in light of empirical evidence from a system without the restrictions that exist in the United States.     

Mapping of murine IgE epitopes involved in IgE-Fc epsilon receptor interactions

The generation of anti-IgE monoclonal antibodies has permitted the identification of various serological epitopes on the IgE molecule. The relationship of the sites on IgE recognized by such antibodies to the Fc epsilon receptor (Fc epsilon R) interaction site has been determined using cross-inhibition studies. However, interpretation of this type of experiment is limited by problems of steric hindrance. Thus, to accomplish precise mapping on the IgE molecule of the Fc epsilon R interaction site and the binding sites of various anti-IgE mAb, we employed site-directed mutagenesis of the IgE heavy chain gene. To this end we have constructed and expressed a recombinant murine constant epsilon heavy chain (C epsilon) gene bearing a (4-hydroxy-3-nitrophenyl)acetic acid (NP)-binding VH region. Several site-specific mutants in the C epsilon 3 and C epsilon 4 domains of this recombinant C epsilon gene were prepared and expressed by transfection into the light chain-producing J558L myeloma cell line. The resulting IgE antibodies were tested for binding to mast cells and to various anti-IgE mAb. The mutants produced include a proline to histidine point mutant at amino acid residue 404 in the C epsilon 3 domain, a mutant with a truncated C epsilon 4 domain, a mutant with a 45 amino acid deletion in the carboxy end of C epsilon 3, and a chimeric human C epsilon in which the human C epsilon 3 was replaced by the homologous mouse C epsilon 3 domain. These mutants have permitted the localization, to the C epsilon 3 domain, of the epitopes recognized by the 84.1C and 95.3 anti-IgE mAb. The 84.1C mAb recognizes a site on IgE which is identical or very close to the Fc epsilon R binding site, and 95.3 recognizes a site on IgE which is related, but not identical to the Fc epsilon R binding site. The antigenic determinant recognized by the 51.3 mAb, which is inefficient at blocking the IgE-Fc epsilon R interaction, has been mapped to the C epsilon 4 domain. When tested for binding to the Fc epsilon R on RBL-2H3 cells, the point mutant bound to the Fc epsilon R with twofold reduced affinity, while the C epsilon 3 deletion mutant and the mutant truncated in C epsilon 4 lost all receptor binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anticholinergic and antiglutamatergic agents protect against soman-induced brain damage and cognitive dysfunction.

Soman, a powerful inhibitor of acetylcholinesterase, causes an array of toxic effects in the central nervous system including convulsions, learning and memory impairments, and, ultimately, death. We report on the protection afforded by postexposure antidotal treatments, combined with pyridostigmine (0.1 mg/kg) pretreatment, against these consequences associated with soman poisoning. Scopolamine (0.1 mg/kg) or caramiphen (10 mg/kg) were administered 5 min after soman (1.2 LD50), whereas TAB (i.e., TMB4, atropine, and benactyzine, 7.5, 3, and 1 mg/kg, respectively) was injected in rats concomitant with the development of toxic signs. Atropine (4 mg/kg) was given to the two former groups at the onset of toxic symptoms. Caramiphen and TAB completely abolished electrographic seizure activity while scopolamine treatment exhibited only partial protection. Additionally, no significant alteration in the density of peripheral benzodiazepine receptors was noted following caramiphen or TAB administration, while scopolamine application resulted in a complex outcome: a portion of the animals demonstrated no change in the number of these sites whereas the others exhibited markedly higher densities. Cognitive functions (i.e., learning and memory processes) evaluated using the Morris water maze improved considerably by the three treatments when compared to soman-injected animals; the following rank order was observed: caramiphen > TAB > scopolamine. Additionally, statistically significant correlations (r = 0.72, r = 0.73) were demonstrated between two learning parameters and [3H]Ro5-4864 binding to brain membrane. These results show that drugs with a pharmacological profile consisting of anticholinergic and antiglutamatergic properties such as caramiphen and TAB, have a substantial potential as postexposure therapies against intoxication by organophosphates.     

Histological evaluation of residual basal cell carcinoma after shave biopsy prior to Mohs micrographic surgery

Background Patients who are referred for Mohs surgery after pre‐operative biopsy has been performed show in some cases no clinical or pathological evidence of tumour persistence. We have previously shown that 25% of these patients show no residual skin cancer either basal cell carcinoma or squamous cell carcinoma. The reasons for ‘disappearance’ of the tumour may be true non‐persistence or false non‐persistence because of wrong‐site Mohs surgery. Objective To determine the incidence of residual basal cell carcinoma after shave biopsy of primary nodular basal cell carcinoma prior to Mohs micrographic surgery. Methods A prospective unblinded study was performed on patients undergoing Mohs surgery for primary nodular basal cell carcinoma. The tumour was removed as a shaved excision using a No. 15 blade at the clinical borders like a shave biopsy (Mohs shave). The bases of the tumors were excised and then sectioned vertically at the middle and cut to the periphery at 10–15 μm intervals till the edge. Results Fifty‐one patients were evaluated. In 40 patients, residual basal cell carcinoma was found at the base of the shave excision site (78.4%). Conclusions Pre‐operative shave biopsy performed during Mohs surgery for primary nodular basal cell carcinoma is ‘curative’ in 22% of the patients.