Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D1 (SCH 23390) or D2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D1 receptor blockade and completely abolished by D2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.     

Symptomatic reversible duodenal compression due to iatrogenic retroperitoneal hematoma

Selective serotonin reuptake inhibitors are frequently employed to treat depression. However, although rarely, coagulation abnormalities have been described following the use of these compounds, and these effects appear to be enhanced by simultaneous use of nonsteroidal anti-inflammatory drugs. We describe a case of reversible symptomatic duodenal compression caused by a retroperitoneal hematoma after ingestion of sertraline and nimesulide.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.     

Low urine citrate excretion as main risk factor for recurrent calcium oxalate nephrolithiasis in males.

To better define the relative role of metabolic factors in the recurrence of stone formation, we studied the 24-hour urinary excretion of calcium (uCa), citrate (uCit), oxalic acid (uOx) and uric acid (uUa) in 73 male patients with primary calcium oxalate urolithiasis. According to the episodes of stone formation per year, we identified 51 recurrent stone formers (RSF) and 22 single stone formers (SSF). 20 normal adult males constituted the control group (C). uCa and uOx were higher in RSF than in C, but quite similar in SSF and RSF. The only difference between RSF and SSF was uCit, significantly lower (2.06 +/- 1.04 mmol/24 h) in RSF than in SSF (3.22 +/- 1.18 mmol/24 h, p less than 0.001) and in C (3.42 +/- 1.33 mmol/24 h, p less than 0.001). Hypocitraturia (uCit less than 1.5 mmol/24 h) was found in 16 of 51 RSF (31.4%) and in 1 of 22 SSF (4.5%). These data confirm that high levels of uCa and uOx represent a risk factor for lithogenesis, but also strongly indicate the low uCit excretion as the most important urinary abnormality accounting for the recurrence of calcium oxalate stones.     

Quality assurance, efficiency indicators and cost-utility of the evaluation workup for liver transplantation.

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost-analysis. A single-center, pre-LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre-LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre-LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre-LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre-LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost-utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of 4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre-LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from 4,710.8 to 4,165.4).     

MM-CK subtypes diagnose reperfusion early after myocardial infarction

Isoelectric focusing (IEF) was used to analyze the serum MM-CK isoenzyme subtypes in 16 patients receiving streptokinase (SK) for attempted coronary thrombolysis early after acute myocardial infarction. Twelve patients had revascularization documented by serial coronary angiograms (Group I); in four patients, angiography documented no such reperfusion (Group II). The data also were compared with a previously reported group of 8 patients who did not receive streptokinase (Group III). Total and MB-CK activity, as well as the MM-CK isoenzyme subtypes MM3-CK, MM2-CK, and MM1-CK tended to rise earlier and peak earlier in Group I compared with Group II; serum MM3-CK, the predominant subtype in myocardium, however, definitely peaked earlier in Group I (8.65 +/- 2.07 hr) compared with Group II (18.50 +/- 6.67 hr) (p less than 0.001). Soon after its release from myocardium, MM3-CK is converted in the serum to MM2-CK and eventually to MM1-CK; thus, the MM3-CK:MM1-CK ratio amplifies the time course of subtype conversion. The MM3-CK:MM1-CK activity ratio peaked earlier in Group I (5.51 +/- 0.97 H) compared to Group II (10.74 +/- 3.28 hr) (p less than 0.01), and peaked even earlier than MM3-CK (p less than 0.007) in both Groups I and II. Thus, the time course of the MM3-CK:MM1-CK ratio separates those patients who reperfuse when early SK is used after acute myocardial infarction from those who do not, and does it significantly earlier than the other enzymatic parameters of cellular necrosis, total CK, and MB-CK.     

Localization of MPP+ binding sites in the brain of various mammalian species

Summary The distribution and density of³H-MPP⁺ binding sites were studied by in vitro quantitative autoradiography in the brain of the mouse, rat and monkey. The highest levels of³H-MPP⁺ specific binding were observed in rat brain. The substantia nigra in rat and monkey, and the anterior caudate-putamen formation in mouse and monkey showed the lowest density of autoradiographic grains. The presence of a relatively high density of MPP⁺ sites in the hippocampus of all species studied could be of interest to explain some effects of MPTP administration on convulsions caused by chemoconvulsants.The finding of a 60–70% reduction of³H-MPP⁺ binding sites in the rat caudate-putamen, on the side of quinolinic acid infusion and no changes after 6-hydroxydopamine lesion of dopaminergic nigrostriatal neurons suggests the presence of these sites mainly on striatal cells.The results suggest that the distribution of MPP⁺ binding sites in brain would not seem to be related to MPTP toxicity.     

Role of thalamic gamma-aminobutyrate in motor functions: catalepsy and ipsiversive turning after intrathalamic muscimol

Bilateral intrathalamic microinjections of nanogram amounts (5–50 ng) of muscimol, a γ-aminobutyrate (GABA) receptor agonist, elicited catalepsy in rats. Like neuroleptic-treated rats, those injected with muscimol in the thalamus remained suspended on a vertical grid but, unlike opioid-treated rats, they failed to remain horizontal on two book-holders. The righting reflex was present, while ptosis was absent. The areas with the highest sensitivity to the cataleptogenic effects of muscimol were the ventromedial and ventral-anterior nuclei of the thalamus. These thalamic areas were also characterized by the shortest latency for the induction of catalepsy. Injection of up to 50 ng of muscimol into the caudate, globus pallidus or entopeduncular nucleus failed to produce catalepsy. Catalepsy was also obtained after intrathalamic microinjection of other GABA analogs, such as 3-aminopropanesulphonic and imidazolacetic acid, which are known to be potent GABA receptor agonists, and β-p-chlorophenyl-GABA , a compound which has GABA mimetic activity. The catalepsy produced by 10 ng of muscimol was reversed by an intrathalamic microinjection of picrotoxin, a GABA receptor antagonist. Muscimol-induced catalepsy, unlike neuroleptic-induced catalepsy, was not reversed by systemic administration of high doses of apomorphine, a dopamine receptor agonist, or of scopolamine, a muscarine antagonist, or by intranigral injection of muscimol, and was not prevented by kainic acid-induced lesions of the striatum or of the nigra. Vice versa, injection of cataleptogenic doses of muscimol in the thalamus failed to prevent the stereotyped gnawing produced by systemic apomorphine or intranigral muscimol. Therefore, in these animals, catalepsy and stereotyped gnawing coexisted. The unilateral intrathalamic microinjection of muscimol resulted in a postural asymmetry consisting of turning towards the injected side. This ipsilateral posturing was converted into an ipsilateral circling by systemic administration of apomorphine.The results indicate that thalamic GABAergic mechanisms play an important role in the regulation of posture and in the mediation of certain motor responses arising in the striatum.