Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward

Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR-12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1-13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS)     

DSM-III-R personality disorders in a mood and anxiety disorders clinic: prevalence, comorbidity, and clinical correlates

This study examined the prevalence, comorbidity, and clinical correlates of personality disorders in an outpatient sample (N = 352) with anxiety and depression. Subjects were diagnosed using the Structured Clinical Interview for DSM-III-R (SCID) on Axes I and II, and they also completed interview and self-report measures of symptoms. Subjects with a personality disorder were less likely to be married, more likely to be single or divorced, had lower family incomes, had more severe symptoms of both anxiety and depression, and had a greater number of lifetime Axis I diagnoses. Subjects with dysthymic and bipolar disorders were more likely, and subjects with panic disorder uncomplicated by agoraphobia were less likely to have a personality disorder compared to the rest of the sample. The most prevalent personality disorders were Avoidant, Obsessive-Compulsive, Paranoid, and Borderline. Paranoid co-occurred with Narcissistic, and Borderline co-occurred with Histrionic personality disorder significantly more often than chance and base rates would predict.     

Histomorphometric study in children with idiopathic nephrotic syndrome

There is agreement on the clinical diagnostic criteria for acute inflammatory demyelinating polyneuropathy (AIDP/GBS) however, there is lack of consensus for detection of demyelination. In order to critically evaluate the prevailing criteria, sixty-six patients who fulfilled NINCDS criteria and had typical features of GBS were studied for electrophysiological abnormalities of peripheral nerves by using standard methods (median, common peroneal, sural and ulnar) between 1 to 12 weeks after the onset of symptoms. The commonest abnormality on motor nerve conduction study was prolonged distal latency (75%-83%) followed by reduction in CMAP amplitude (63%-82%), decreased velocity (48%-62%), conduction block (17%-39%) and f-wave abnormalities (37.8%-59%). Sensory conduction abnormalities were detected in over 20% of median, 25% of ulnar and 33% of sural nerves. All the patients had abnormality of at least two motor conduction parameters in one nerve when values beyond 2 SD of the mean were considered abnormal and over 70% of patients had three abnormalities in two nerves or two abnormalities in three nerves. Comparison with the prevailing criteria for demyelination revealed that the number of patients fulfilling them varied widely: Albers et al. (1985): 74.2%, Albers et al. (1989): 40.9% and Cornblath: 30.3%. We believe that the current criteria for detection of demyelination in acute neuropathy are too strict, underestimate the underlying pathology in GBS and need reassessment.     

Reaffirming professionalism through the education community

OBJECTIVE: To determine the role of the clinical training environment and a medical education community in reaffirming medical professionalism among physicians-in-training and faculty. DATA SOURCES: Published articles on undergraduate and graduate medical education and sociology works on professionalism were identified through research. STUDY SELECTION: Studies were selected that illustrated barriers to professionalism in medical education and patient care and the professional conduct of medical students, residents, and faculty. RESULTS: Factors that undermined the medical education community were the specialization of medicine, the faculty reward systems, and the service demands of residency because of the economics of health care. CONCLUSIONS: Establishment of a firm system with a core teaching faculty, creation of mentoring and role modeling programs, implementation of a longitudinal curriculum on medical professionalism, evaluation of physicians on professional conduct, and evaluation of the clinical training environment are suggested as strategies to re-establish an education community and reaffirm professionalism in medicine.     

European medical schools and tobacco

Following a survey in 19 European countries of the habits, attitudes and knowledge of medical students regarding tobacco, World Health Organisation European Office and the International Union against Tuberculosis and Lung Disease jointly circulated to the Deans of all European medical schools a summary of the results, including figures for mortality for smoking-related diseases in their countries and a brief questionnaire concerning faculty action on the tobacco problem. The response rate was just over 50%, higher in Northern Europe (66%) than in Southern (35%) or Eastern (38%). Only 8% of faculties had a specific teaching module on tobacco. In most it was either systematically (35%) or unsystematically (55%) integrated in other teaching. Teaching hospitals, teaching areas and faculty meetings were said to be smokefree by over 90%; figures were lower for other areas. Seventy-seven per cent of Deans intended to discuss our approach with their teaching staff; 72% gave the name of a staff member with a particular tobacco interest.     

Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites

OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.     

Definitive or exploratory periodontal experimentation: an overview of the literature

Definitive and exploratory randomized controlled trials (RCTs) have different goals as well as different design and analysis characteristics. The goal of definitive studies is to provide unequivocal evidence of a treatment's tangible benefit to the patient; a pre-trial-specified hypothesis is tested by use of a pre-trial-specified method. The goal of exploratory studies is to elucidate biological treatment mechanisms, to identify promising treatments, and to generate hypotheses for definitive studies: multiple hypotheses are evaluated to extract as much information from the data as possible. The purposes of this study were: (1) to survey selected design and analysis characteristics of randomized controlled periodontal trials published between 1988 and 1992 (n = 86), and (2) to classify trials as exploratory or definitive studies. The periodontal RCTs surveyed were typical of exploratory studies whose primary goal was to elucidate biological treatment mechanisms. Trial reports indicated the testing of multiple hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in 67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and design and analysis characteristics (e.g., an absence of masking in 57 out of 86 trials) were also typical of exploratory studies which strive to obtain quick answers (short duration) at a low cost (small sample size; accept bias for increased efficiency and a lower cost). No definitive trials were identified. Promising, biologically active, treatments identified in exploratory trials should be evaluated in definitive studies where the primary goal is the procurement of unequivocal evidence of a treatment's tangible benefit to the patient. The costs and benefits of conducting definitive periodontal RCTs to provide such evidence should be investigated.