Maintenance of amphetamine-induced stereotypy and locomotion requires ongoing dopamine receptor activation

Amphetamine-induced locomotion and stereotypy depend on dopamine (DA), yet, while extracellular DA concentrations peak early, and then begin to decline, intense stereotyped behaviors continue for relatively prolonged periods. These observations suggest that DA may act as a “trigger” for the entire multi-phasic behavioral response. To test this hypothesis in rats, haloperidol (HAL) was injected at different times with respect to (AMPH), and automated and videotaped measures of the behavior were recorded. HAL (0.1 mg/kg, IP) or saline was administered either 15 min prior to AMPH (4.0 mg/kg, SC); 60 min following AMPH (during the phase of intense oral stereotypy); or 140 min after AMPH (during post-stereotypy locomotion). When administered prior to AMPH, HAL prevented the development of stereotypy, and an increase in locomotion was displayed in place of stereotypy. Haloperidol administration during stereotypy interrupted the response, and resulted in an increase in locomotion for the remainder of the stereotypy phase. In neither of these cases did HAL affect post-stereotypy locomotion. However, when injected during the post-stereotypy phase, HAL caused a decrease in the magnitude of the locomotor response, suggesting that both the stereotypy and locomotor components of the response remain sensitive to HAL at times when DA levels have significantly declined. These results do not support the hypothesis that the early increase in extracellular DA produced by AMPH, acts as a “trigger” for a non-dopaminergic receptor-mediated expression of the later phases of the AMPH response. Instead, it appears that both stereotypy and post-stereotypy locomotion remain sensitive to DA receptor blockade when extracellular DA levels are below the levels produced by non-stereotypy-inducing doses of AMPH. Received: 15 August 1996/Final version: 24 October 1996     

Practice patterns of physician members of the American Urogynecologic Society regarding female sexual dysfunction: results of a national survey

The purpose of the study was to evaluate practice patterns of members of the American Urogynecologic Society (AUGS) with respect to female sexual dysfunction (FSD). A brief self-administered survey of 20 questions was mailed to 966 physician members of the AUGS in the United States of America and Canada; 471 surveys were returned (49% response rate). The majority of responders see urogynecology (19%) or urogynecology and general gynecology patients (43%). Sixty-eight percent of physicians were familiar with questionnaires to assess FSD; however, only 13% said they use these for screening purposes. Most said they believed screening for FSD was somewhat (47%) or very important (42%). Despite having these beliefs, only 22% of the responding physicians stated they always screen for FSD, while 55% do so most of the time and 23% admitted they never or rarely screen. Similar results were obtained regarding screening following urogynecologic surgery. Several barriers to screening for FSD existed, the most common being lack of time. The majority of respondents (69%) underestimated the prevalence of FSD in their patient population. Finally, although more than half of responders had received post-residency training in urogynecology (59%), 50% of them stated the training with respect to FSD was unsatisfactory, while only 10% were satisfied. Overall, many urogynecologists do not consistently screen for FSD, underestimate its prevalence, and feel they received unsatisfactory training.     

The use of systolic pressure variation in hemodynamic monitoring during deliberate hypotension in spine surgery

The systolic pressure variation (SPV), which is the difference between the maximal and minimal systolic blood pressure (SP) during one ventilatory cycle, was studied in ten patients during posterior spine fusion. To minimize the blood loss, deliberate hypotension to a mean blood pressure of 50 mmHg was introduced by a continuous infusion of sodium nitroprusside. SPV was further divided into two components, delta up and delta down, using SP during a short apnea as a reference point. All hemodynamic parameters were measured at the beginning of anesthesia, 15 minutes after induction of hypotension, before cessation of nitroprusside infusion, and 15 minutes after the end of the hypotensive period. During the hypotensive period (166 +/- 53 minutes), cardiac output (CO) decreased significantly from 4.83 +/- 1.36 L/min to 3.86 +/- 1.07 L/min (p less than 0.05). Heart rate (HR), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) did not change during this period and bore no correlation to the changes in CO. The only variables that changed during the hypotensive period, in addition to CO, were SPV (from 13.1 +/- 4.9 mmHg to 16.9 +/- 5.1 mmHg, p less than 0.02), and delta down (from 6.0 +/- 3.8 mmHg to 9.9 +/- 6.3 mmHg, p less than 0.05). The delta down segment was the only hemodynamic variable whose changes during the hypotensive period showed a significant (p less than 0.018) correlation with the changes in CO. delta down reflects the degree of decrease in left ventricular stroke output in response to a positive pressure breath, and thus is a sensitive indicator of preload.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of radiation on the production of interleukins and T-lymphocyte activities

The effect of 0-400 rad 60Co gamma-ray doses on distinct steps in the process of murine T-cell activation by concanavalin A (Con A) was investigated. When C57BL/6 spleen cells were stimulated immediately after irradiation, production of interleukin-1 (IL-1) and interleukin-2 (IL-2) was not impaired. Concomitantly, the display of IL-2 receptors in Con A-induced reactivity to IL-2 was not affected. The proliferative response was markedly diminished by increasing doses of radiation. The effect of radiation was found to depend not only on the delivered dose but also on the time interval between irradiation and stimulation of the lymphoid cultures. When the mitogenic stimulus was delayed for 24 hours following irradiation, IL-1 production was not diminished, whereas IL-2 production was impaired by doses greater than 200 rad. The proliferative response was diminished to a markedly higher degree as compared to the degree it was diminished in cell cultures stimulated by Con A immediately after irradiation. IL-2 production and the proliferative response to Con A of irradiated cell suspensions, cultured without mitogen for 24 hours post irradiation, were also assessed after adjustment for cell death. In this case, an impairment in IL-2 production that was dose dependent was apparent, but still the levels of IL-2 secreted by 400-rad irradiated cells reached high levels. In contrast, the proliferative response to Con A could not be restored. When T-cell growth factor was added concomitantly with Con A to irradiated cell cultures, a radioprotective effect could be observed.     

Nitric oxide-related species inhibit evoked neurotransmission but enhance spontaneous miniature synaptic currents in central neuronal cultures

Nitric oxide (NO^·) does not react significantly with thiol groups under physiological conditions, whereas a variety of endogenous NO donor molecules facilitate rapid transfer to thiol of nitrosonium ion (NO⁺, with one less electron than NO^·). Here, nitrosonium donors are shown to decrease the efficacy of evoked neurotransmission while increasing the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs). In contrast, pure NO^· donors have little effect (displaying at most only a slight increase) on the amplitude of evoked EPSCs and frequency of spontaneous mEPSCs in our preparations. These findings may help explain heretofore paradoxical observations that the NO moiety can either increase, decrease, or have no net effect on synaptic activity in various preparations.     

Child and adolescent electroconvulsive therapy: a case report.

Electroconvulsive therapy (ECT) is a controversial treatment modality that is only rarely performed on children and adolescents. There is a marked paucity of published data relating to the indications, use, clinical outcome and complications of ECT in this age group. The ethical and moral issues surrounding the use and in particular the research of ECT in this group of patients makes controlled data very difficult to come by. The following case report and review of the literature will address some of these issues.     

Split-thickness skin excision in severe open fractures

Split-thickness skin excision can be used as a one-stage procedure for the accurate diagnosis of flap viability and the immediate treatment of friction-avulsion injuries in severe open fractures. After cleaning the wound, the avulsed flap is temporarily sutured back to its original bed and a split thickness graft is taken from it and meshed to a 1:3 ratio. Surface dermal capillary bleeding then serves as an indicator of viability, clearly displaying a line for the excision of devascularized skin and correlating well with a concomitant fluorescein test. The wounds are re-opened and, after fixation of the fracture, the viable part of the flap is returned to its original bed and the remaining defects are covered with the meshed graft. We have treated 16 patients with extensive degloving injuries in this way, 15 needing only the single surgical procedure. All retained flaps survived, no other donor sites were needed and the split-thickness grafts took with 90% to 100% success.     

Radiotherapy planning: direct tumor location on simulation and port films using CT. Part I. Principles

Although there have been great advances in cancer diagnosis in recent years, it remains difficult to transfer tumor location information from cross-sectional computed tomographic (CT) scans or magnetic resonance images to the simulation and verification films used in planning radiotherapy. A newly developed system uses radioopaque markers attached to the patient as reference points. These markers are identified on both CT scans and simulation films and their locations entered into the treatment planning computer. The tumor and any desired normal structures are then outlined manually on each CT section. Transparent overlays produced by the computer show the position of the reference markers and tumor outlines for any combination of gantry angles and source-film distance. Because the overlays are scaled to the simulation films, the reference points enable precise alignment of overlay and film. The tumor outline thus appears on the simulation or verification films exactly as it is "seen" by the therapy beam, making field verification straightforward and accurate, even on oblique films.     

Targeting of anti-tumor responses with bispecific antibodies.

T cells can be induced to specifically lyse tumor cells with bispecific antibodies containing anti-T cell receptor mAbs crosslinked to anti-tumor mAbs. Such "targeted cytolysis" requires that the target cell be bound directly to the cytotoxic cell. In addition, targeted T cells mediate a second activity, the secretion of factors that can block the growth of both tumor target cells and bystander tumor cells. When given to nude mice bearing intraperitoneal human ovarian carcinoma, targeted human T cells cause the rapid removal of most tumor cells from the peritoneum, and markedly prolong the times of survival of treated mice. The efficacy of targeted T cells for treating human cancer is currently being tested in clinical trials.