Space and imagery, the individual in space, space in the individual]

Starting from the phenomenological analysis of perception and of representation made by Jaspers, and from a poem of the German poet Mathias Claudius, the author displays rapidly the emergency of the subject in the space, with the progressive development of the corporal sketch. If the child learns with difficulty to recognize other people, he will have need of a much longer time to recognize his own corporal unity in the mirror stage. That first recognition of his unity is imaginary and creates the interior space. With other people's presence, a relation of reciprocity settles, and the desire of the other one appears. Since Freud, the notion of desire is well known, it has allowed to understand better relation between outside space, where other people stay, and inside space of the subject and the whole relational dynamics between themselves. Jung has completed that analysis by showing the role of archetypical images in psychic life; he has emphasized "I" dialectics and the Unconscious. Phenomenological analysis of the meeting allows a better knowledge of the role of the sexual body in the exchange with the other one, mediated by the look as well as by the language, but also opening the subject to the gap of incompleteness. Our being-in-situation makes us discovering the distance that can only be filled up by Love. That limitation of being and that displacement in Love union have been praised by poets and celebrated by mystics.     

Effects of Electroconvulsive Therapy on the Electrocardiogram in Geriatric Patients with Stable Cardiovascular Diseases

Eight elderly patients (mean age +/- SD, 73.2 +/- 9.5 years) were studied with Holter electrocardiographic monitoring for 24 h before and 24 h after an electroconvulsive therapy (ECT) treatment. Patients with a history of cardiac disease but who were not experiencing any active cardiac symptoms were chosen for study. They were not receiving either cardioactive medications or psychotropic agents that can effect cardiac rhythm or conduction. Each patient served as his own control, with direct comparison of the periods before and after the treatment. There were no differences before and after ECT in the electrocardiogram. One minute after the seizure, patients were hypertensive and tachycardic. ECT does not appear to pose additional risk in stable, elderly patients with a history of cardiac disease.     

Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways

We recently described the cloning of a fifth member of the 5-hydroxytryptamine (5-HT)₁ (serotonin₁) receptor class that inhibits adenylyl cyclase, namely the human 5-HT_1F receptor (Adham et al. 1993 a). In the present study we have examined in greater detail the functional coupling of the 5-HT_1F receptor in two different cell lines, NIH-3T3 and LM(tk^–) fibroblasts (receptor densities of 1.7 and 4.4 pmol/mg protein, respectively). The maximal inhibitory response elicited by 5-HT was significantly greater in NIH-3T3 as compared to LM(tk^–) cells, whereas the EC₅₀ values were comparable.To investigate the relationship between receptor occupancy and inhibition of cAMP accumulation mediated by 5-HT_1F receptors in NIH-3T3 cells (and hence the degree of receptor reserve), we used the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The half-maximal response required only about 10% receptor occupancy, consistent with a receptor reserve of 90% (88±2.1%, n = 4) for 5-HT-induced inhibition of FSCA. Despite the presence of such a high degree of receptor reserve, a range of intrinsic activities was displayed by structurally diverse classes of compounds. For example, sumatriptan and lysergol were as efficacious as 5-HT itself and thus acted as full agonists, whereas metergoline and 1-NP behaved as partial agonists and as shown previously (Adham et al. 1993a), methiothepin was a silent antagonist (K_b = 438 nM).We have also investigated activation of additional signal transduction pathways by the 5-HT_1F receptor and found that the responses differ in the two cell lines with respect to stimulation of phospholipase C. For example, in NIH-3T3 cells no elevation of inositol phosphates (IP) of [Ca²⁺]_i was observed even at very high agonist concentrations (100 M). In contrast, in LM(tk^–) cells concentrations of 5-HT as low as 10 nM induced stimulation of IP and a rapid increase of [Ca²⁺]i. The 5-HT_1F receptor failed to alter arachidonic acid release in either cell line.The maximal increase in IP accumulation in LM(tk^–) cells was modest, averaging about 100% above basal. The increases of IP and [Ca²⁺]_i required 5-HT concentrations less than one order of magnitude greater than those inhibiting FSCA (EC₅₀ = 17, 55 and 8 nM, respectively), and both responses were blocked by 100 M methiothepin. All three responses (cAMP, IP, and [Ca²⁺]_i) were sensitive to pertussis toxin pre-treatment, suggesting the involvement of G_i/G_o protein(s) in these signal transduction pathways. [Ca²⁺]_i was also elevated by sumatriptan, which may provide a mechanism by which this drug causes constriction of the vasculature. In conclusion, these data indicate that the human 5-HT_1F receptor can couple to multiple effectors, and that this coupling is cell-type dependent.Abbreviations FSCA forskolin-stimulated cAMP accumulation - [Ca²⁺] intracellular free calcium concentration - AA arachidonic acid - EEDQ N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline - CHO chinese hamster ovary cell - LM(tk^–) mouse fibroblast cell - B_max maximal binding site density - K_i apparent dissociation constant obtained from competition binding studies - G protein guanine nucleotide-binding protein - HBS HEPES-buffered saline - IP inositol phosphates - IP₃ inositol 1,4,5 trisphosphate - PLC phospholipase C - K_b antagonist dissociation constant - K_d equilibrium dissociation constant - N-1F-6 stable NIH-3T3 cells expressing the cloned 5-HT_1F receptor - L-1F-3 stable LM(tk^–) cells expressing the cloned 5-HT_1F receptor - PTX pertussis toxin - BSA bovine serum albumin - METH methiothepin - SUMA sumatriptan - 5-MeO-DMT 5-methoxy-N,N-dimethyltryptamine - 1-NP 1-(1-napthyl)piperazine - 5-CT 5-carboxyamidotryptamine Correspondence to: N. Adham at the above address     

An Evaluation of Breastfeeding Promotion Through Peer Counseling in Mississippi WIC Clinics

Objective: This study evaluates the effectiveness of a peer counseling program at increasing breastfeeding by participants in the Mississippi Special Supplemental Nutrition Program for Women, Infants and Children (WIC). Methods: Data from the 1989–1993 Pediatric Nutrition Surveillance System were analyzed to compare breastfeeding rates in clinics with and without peer counseling programs. A questionnaire completed by program staff to describe the program in greater detail helped identify characteristics associated with greater success. Results: The incidence of breastfeeding rose from 12.3% to 19.9% in those clinics with peer counseling programs, but only from 9.2% to 10.7% in clinics without a program. Clinics that started a program earlier showed greater changes in breastfeeding incidence. However, the presence of lactation specialists or consultants in the clinic appeared to be more important than the presence of less-trained peer counselors. Peer counselors who spent more than 45 minutes per participant were more effective than those spending less time. Conclusions: The peer counseling program significantly increased the incidence of breastfeeding, particularly in clinics with lactation specialists and consultants. Success can be enhanced by ensuring that peer counselors spend a great deal of time with the participants.     

Aromatase inhibitor development for treatment of breast cancer

Summary Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue.To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hrurine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples. These data suggest that CGS 20267 can be expected to bring improved response rates in the treatment of metastatic hormone-dependent breast cancer without substantial side effects.Presented by R.J. Santen at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, November 4, 1993; Mini-symposium on New Agents in Breast Cancer (supported by an educational grant from Rhône-Poulenc Rorer).     

Clean Intermittent Catheterization in Boys Using the Lofric Catheter

Purpose

We compared a recently developed hydrophilic catheter to the standard polyethylene catheter in regard to hematuria, infection and patient satisfaction.

Materials and Methods

A hydrophilic LoFric^* or standard Mentor^† catheter was assigned at random to 17 and 16 boys, respectively, who were skilled in intermittent self-catheterization. They were evaluated by weekly urinalysis and a questionnaire.

Results

Significantly fewer episodes of microscopic hematuria occurred in the LoFric than Mentor catheter group (9 episodes in 6 subjects versus 19 episodes in 11, p less than 0.05). There were also fewer episodes of bacteriuria in the LoFric group but the difference was not statistically significant. Mean scores plus or minus standard deviation on a visual analogue scale with 0 equal to most and 10 equal to least favorable were LoFric 3.3 plus/minus 2.8 versus Mentor 4.9 plus/minus 2.7 for catheter convenience and 2.7 plus/minus 2.4 versus 4.2 plus/minus 2.6 for insertion comfort, significantly favoring the LoFric group (p less than 0.05 for both). Of the 16 LoFric subjects 13 preferred to continue its use, particularly those with a history of urethral trauma or sphincteric spasm.

Conclusions

In boys the LoFric catheter appears to cause less trauma. Although it is not reusable and is more expensive than the standard catheter, satisfaction is higher with the LoFric device and for select patients it has significant advantages.     

Clinical Guidelines Panel on Erectile Dysfunction: Summary Report on the Treatment of Organic Erectile Dysfunction

Purpose

The American Urological Association convened the Clinical Guidelines Panel on Erectile Dysfunction to analyze the literature regarding available methods for treating organic erectile dysfunction and to make practice recommendations based on the treatment outcomes data.

Materials and Methods

The panel searched the MEDLINE data base for all articles from 1979 through 1994 on treatment of organic erectile dysfunction and meta-analyzed outcomes data for oral drug therapy (yohimbine), vacuum constriction devices, vasoactive drug injection therapy, penile prosthesis implantation and venous and arterial surgery.

Results

Estimated probabilities of desirable outcomes are relatively high for vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis therapy. However, patients must be aware of potential complications. The outcomes data for yohimbine clearly indicate a therapy with marginal efficacy. For venous and arterial surgery, based on reported outcomes, chances of success do not appear high enough to justify routine use of such surgery.

Conclusions

For the standard patient, defined as a man with acquired organic erectile dysfunction and no evidence of hypogonadism or hyperprolactinemia, the panel recommends 3 treatment alternatives: vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis implantation. Based on the data to date, yohimbine does not appear to be effective for organic erectile dysfunction and, thus, it should not be recommended as treatment for the standard patient. Venous surgery and arterial surgery in men with arteriolosclerotic disease are considered investigational and should be performed only in a research setting with long-term followup available.     

Crisnatol mesylate: Phase I dose escalation by extending infusion duration

Summary Crisnatol mesylate is a rationally designed cytotoxic arylmethylamino-propanediol with broad spectrum cytotoxic activity. A phase I study with an unconventional escalation scheme was developed using a constant drug infusion rate (mg/m²/hr) and prolonging the infusion duration from 6 to 96 hours. Sixty-five patients received crisnatol at doses from 18 mg/m² in 6 hrs to 3400 mg/m² in 72 hours. The dose-limiting toxicity in two of five patients at 2700 mg/m² and two of three patients at 3400 mg/m² was neurologic and consisted of a syndrome of confusion, agitation, and disorientation. Phlebitis mandated the use of a central line. The mean terminal phase half-life (T_1/2 ) was 3.3 hours with a total body clearance (CL) of 22.8 L/hr/m² and a volume of distribution (Vd_ss) of 53 L/m². The median steady-state peak plasma concentration (C_ss) at 2700 mg/m²/72 hours was 2.7 g/ml and at 3400 mg/m²/72 hours was 3.8 g/ml. No responses were seen. The maximum tolerated dose (MTD) on this schedule is 2700 mg/m²/72 hours in patients with no liver disease and good performance status.     

Polyamine involvement in the secretion and action of TGF-α in hormone sensitive human breast cancer cells in culture

These experiments were designed to test polyamine (PA)* involvement in the secretion and action of transforming growth factor (TGF-) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E₂) and TGF- stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E₂-stimulated growth, administration of the PA synthesis inhibitor -difluoromethylornithine (DFMO) did not influence either basal or E₂-induced TGF- secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-. However, when the culture conditions were changed to serum-free medium, TGF- and E₂-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E₂-stimulated TGF- secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF- and E₂-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells.