Effects of neuroleptics on rate and duration of operant versus reflexive licking in rats

Operant conditioning techniques were used to train one group of nine rats to lick a dry horizontal metal disk on a fixed ratio 15 schedule with water reinforcement delivered at a different location. Another group of seven rats licked reflexively from a water reservoir positioned with the same spatial arrangements as the metal disk. The distance the rats' rongues traversed (10 mm) to contact the licking surface was the same in both the operant and reflexive lick conditions. The effects of three neuroleptics, haloperidol (0.06, 0.12, 0.24, 1.0, 2.0 mg/kg), chlorpromazine (0.5, 1.0, 2.0 mg/kg) and clozapine (2.5, 5.0, 7.5 mg/kg) on average lick rate and median lick duration were assessed for both groups. Dose related decreases in average lick rate were observed in both groups of rats as a function of dose of each of these neuroleptics. Moreover, operant lick rates were proportionately more affected by neuroleptic treatment than were reflexive lick rates. The dose-response effect for the duration variable was different for the two lick conditions in that reflexive lick duration was lengthened as dose increased, whereas operant lick duration was lengthened only at the lower doses of these drugs. The differential effect of these neuroleptics on operant vs. reflexive licking suggests that neuroleptics attenuate selectively those responses that require relatively more conditioning to acquire. These results may be analogous to the initiation deficit that has been suggested to account for neuroleptics' selective attenuation of avoidance, while leaving relatively intact the escape response in escape/avoidance procedures.     

The presence of polyglucosan bodies in temporal lobe epilepsy: its role and significance

RATIONALE: Mesial temporal sclerosis (MTS) is an important pathology in temporal lobe epilepsy (TLE) and often associated with good surgical outcome, however prognostic factors for surgical outcome are conflicting. The authors examine seizure outcome after surgery for TLE due to MTS, with focus on the presence of polyglucosan bodies (PGBs), and its relation to the epileptogenic process. METHODS: Records of 44 consecutive patients with intractable TLE who underwent anterior temporal lobectomy (ATL) at JFK medical center between 1994-2001 were reviewed. Details of clinical, electrophysiological evaluation, and outcome were collected. All slides were reviewed for the presence of MTS. In twenty-one patients with MTS, detailed histology of surgical specimens was reviewed and relative concentration of PGBs was assessed. The postoperative follow-up duration ranges between 28-74 months. Surgical outcome was evaluated according to Engel's classification. RESULTS: Data of fourteen females (mean age 32.8 years) and 7 males (mean age 34.2) were analyzed. PBGs were identified in 10 patients (8 females and 2 males). All 10 patients had good surgical outcome, with 6 patients (60%) being seizure free (class 1) and 4 patients as class 2. While 11 patients (6 males and 5 females) with absent PGB, 72.8% had good surgical outcome. Of these, 7 (63.8%) had class 1, 1 patient had class 2, and 3 patients had class 3&4. Assessing several risk factors, the only significant difference between the two groups was epilepsy duration, which was significantly longer in patients with PGBs (P = 0.011). CONCLUSION: The histological presence of PGB is associated with long duration of epilepsy and could be the consequence of epilepsy. Despite prolonged duration of epilepsy, the surgical outcome in PGBs +ve is similar to PGBs -ve patients.     

The effect of duration of cerebral ischemia on brain pyruvate dehydrogenase activity, energy metabolites, and blood flow during reperfusion in gerbil brain

The objective of this study was to determine whether the duration of an ischemic insult effects the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) in relation to the recovery of metabolites and regional cerebral blood flow (rCBF) immediately after ischemia and during reperfusion in gerbil cortex. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 20 or 60 min, followed by reperfusion up to 120 min. Immediately after ischemia PDH activity increased threefold regardless of ischemic duration. In the 60-min ischemic group, PDH remained activated, the recovery of high energy phosphates and the clearance of lactate were poor, and the rCBF was 48% of controls after 20-min reperfusion, decreasing gradually to 26% at 120-min reperfusion. In the 20-min ischemic group, PDH activity normalized quickly, the restoration of energy phosphates was good, there was a quick reduction in lactate within the first 60 min of reperfusion, and the rCBF was 65% of control at 20-min reperfusion, and remained over 48% of control throughout reperfusion. Recovery of metabolism after reperfusion did not parallel the changes in rCBF in either group, most noticeably in the 60-min ischemic group. The slow normalization of PDH activity reflected the poor recovery of metabolites in the 60-min ischemic group, indicating that PDH activity is important in the resynthesis of energy metabolites during reperfusion. In conclusion, prolonging the ischemic insult effected PDH activity during reperfusion, impaired recovery of energy metabolites, and worsened the recovery of rCBF.     

Lacidipine: effects on vascular pressor responses throughout the dosage interval in normotensive subjects

Aims To assess the duration and consistency of the pharmacological activity of the dihydropyridine calcium antagonist drug, lacidipine.
Methods Eight healthy normotensive young males participated in a double-blind randomised crossover comparison of single and multiple doses (for 2 weeks) of lacidipine and placebo. The calcium antagonist effects were quantified at 2, 6 and 24  h post dose by the extent of the attenuation of the pressor responses to the intravenous administration of the vasoconstrictors angiotensin II and noradrenaline.
Results After 2 weeks of treatment, lacidipine consistently and significantly attenuated the pressor responses to both agents at 2  h post dose. At 6 and 24  h post dose there was a significant and progressive decline in the effectiveness of lacidipine in attenuating the pressor responses and for the response to angiotensin II there was no statistically significant effect at either 6 or 24  h post dose.
Conclusions These results indicate that there is an obvious 'peak' in the pharmacological activity of lacidipine at about 2  h post dose and that this activity is not fully and consistently maintained throughout 24  h.     

Infertility after 8 years of marriage: a pilot study

With the objective of measuring the prevalence and durationof infertility in a developing country, a retrospective cross-sectionalstudy was designed. The survey was conducted at the Departmentof Obstetrics and Gynaecology, Hospital Sn. Borja-Arriaran,Mother and Child Research Institute, University of Chile, Santiago,March–September 1990. The study population comprised 474women 15–45 years old selected at random from the 11 289weddings that took place in downtown Santiago, Chile, in 1982.The reproductive history for the preceding 8 years was obtainedthrough home interviews with the women conducted by midwives.The main outcome measures were the prevalence and duration ofinfertility. The results in this sample showed a 7.04% (95%confidence interval 6.21–7.87) prevalence of infertilityafter 8 years of marriage with a mean duration of 23 months.It is concluded that after 8 years of marriage about one outof 25 women is infertile (4.01%). This identified a group ofpatients that would benefit from a programme of assisted reproductivetechnology.     

Rate-dependent failure of ventricular capture in patients treated with oral propafenone.

The effects of propafenone on ventricular excitability were studied in 18 patients after 9 +/- 6 days on oral propafenone (900 mg/day). Late diastolic double threshold right ventricular stimulation was performed at variable rates. In five patients (28%, group I) an intermittent, rate-dependent failure of ventricular capture was reproducibly observed during stimulation at rates above the sinus rhythm but not exceeding 150 beats min-1. In four patients loss of capture was preceded by gradual prolongation of the interval between the stimulus artifact and the local right ventricular bipolar electrogram. Such findings were not observed in the remaining 13 patients (group II) on propafenone nor in 28 studies in the same patients on different antiarrhythmic agents. Group I vs group II patients were older (72 +/- 4 vs 53 +/- 18 years, P = 0.002), had longer right ventricular effective refractory periods on the baseline (P = 0.004) and on propafenone (P = 0.0003), and had longer QRS duration on propafenone. The increase produced by propafenone in sinus rhythm QRS duration, paced QRS duration and ventricular effective refractory period was greater in group I than in group II: 42 +/- 36 vs 14 +/- 12 ms, P = 0.01, 94 +/- 43 vs 34 +/- 26 ms, P = 0.0002, 88 +/- 64 vs 22 +/- 37 ms, P = 0.025, respectively. Thus propafenone can produce rate-dependent failure of ventricular capture which is associated with marked prolongation of refractoriness and QRS duration suggesting a marked use-dependent drug effect in selected patients.     

Characteristics of the plasma melatonin rhythm are not modified by steroids during the estrous cycle in Ile-de-France ewes

Abstract: Two experiments were designed to determine whether gonadal steroids during the estrous cycle may modify the characteristics of the plasma melatonin rhythm. In the first experiment, 12 ovariectomized estradiol-treated ewes were used and exposed to constant short days. The experimental design was a latin square to distinguish between steroid treatments and individual effects on melatonin secretion. Twenty four hours before the bleeding period (hourly during 20 hr) and with a 1 week interval, animals were treated with a) additional subcutaneous estradiol implants, b) progesterone devices, or c) control. In the second experiment, nine ewes received a treatment combining fluorogestone acetate devices and pregnant mare serum gonadotrophin to induce synchronous ovulations. Samples for melatonin determination were obtained hourly for 13 hr at three stages of estrous cycle: follicular phase, early luteal phase, and late luteal phase. Ovarian activity was monitored by taking daily samples for progesterone analysis and ovulation rate was determined by laparoscopy. Duration and mean melatonin plasma concentrations of the elevation were calculated for each ewe and each night and analysed by latin square test (experiment 1) or ANOVA (experiment 2). Melatonin concentrations of elevation and duration of elevation were not significantly affected by hormonal treatments or by phase of estrous cycle. A strong individual effect was detected ( P <0.01) for both parameters in both experiments. It was concluded that melatonin secretion is unaffected by steroid administration or by phase of estrous cycle. The existence of very high inter-individual variation suggest that both parameters are individual characteristics of each animal which may have a strong genetic basis.     

Age of onset and duration of dementia in people with down syndrome: Integration of 98 reported cases in the literature

The published case reports of 98 people with Down Syndrome were studied with respect to the age of onset and duration of clinically diagnosed dementia. The incidence of dementia was unimodal, increasing rapidly from 40 years to a peak of 30% incidence in the fifth decade of life, followed by a further rapid decline. Females with Down syndrome had an earlier onset. Duration of dementia decreased with increasing age of onset for both males and females.     

Dose intensification in acute myloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's ATML9 study

Between 1984 and 1990, 972 patients aged 1–79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1+5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3+10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2+7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3+10 regimen than with DAT 1+5 (13% v 23%; P==0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P=0.15). Moreover, CR was achieved more rapidly with DAT 3+1 (median 34 v 46 d; P<0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P=0.05) and survival (23% v 18%; P<0.05) were also better with DAT 3+10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P=0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of out-patient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3+10, is not only more effective than DAT 1+5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.     

Some characteristics of saccadic eye movements in children of primary school age

The characteristics of saccadic eye movements have been extensively studied in adults; researches have also been devoted to the saccades of preschool age children. On the contrary, for primary school-age children no data exist; we investigate the eye movements (recorded utilizing an infrared technique) of six children 7 to 11 years old. The main results indicate that the values of some parameters (for example the saccadic latency and duration) are in the same range as the values of the correspondent parameters in adults, while the values of other parameters (in particular peak velocity and mean velocity/peak velocity ratio) are distinctly different from the ones measured in adult subjects.