Chronic morphine-induced hyperactivity in rats is altered by nucleus accumbens and ventral tegmental lesions

Lesions of the nucleus accumbens (NA) and the ventral tegmental area (VTA) attenuated and delayed the onset of the locomotor excitatory effects of morphine following chronic administration. Neither lesion, however, totally prevented the increase in locomotor excitation. These findings suggest that while the NA and VTA seem to play a role in mediating the excitatory effects of morphine, other regions and brain circuits must also be involved.     

The natural history of anterior cruciate ligament reconstruction using patellar tendon autograft

The purpose of this study was to review the results of ACL reconstruction using a patellar tendon graft placed ‘over the top’ plus a Macintosh lateral tenodesis, examining changes in knee laxity and functional status with increasing time. There were 74 patients operated on over an 11 year period, and divided into four groups for analysis according to postoperative time. There was a significant and progressive increase in side-to-side laxity difference with time, although functional status did not change significantly, indicating a lack of correlation between objective clinical tests and subjective findings. The highest Lysholm, Tegner and IKDC scores were at 4–5 years after operation, when 60% of patients were at their pre-injury level of sports activity. However, there was always a very significant difference between actual and desired Tegner activity levels for the group as a whole. While there was a significant correlation between degenerative changes and the time between injury and reconstruction, there was no correlation with postoperative time: this provides evidence that ACL reconstruction can protect the knee from later degeneration.     

Enhancement of NMDA-induced current by the putative NR2B selective antagonist ifenprodil

Ifenprodil has been widely used as an antagonist selective for NMDA receptors containing the NR2B subunit. Evidence suggests, however, that ifenprodil also increases NMDA receptor affinity. Using rat brain slices, we found that ifenprodil enhanced NMDA-induced current in both cortical and subcortical areas examined. To test whether the effect is due to an increase in NMDA receptor affinity, we compared the effect of ifenprodil on currents induced by different concentrations of NMDA. Consistent with the hypothesis, the enhancing effect (percent increase) was relatively constant at low NMDA concentrations. As NMDA concentration increased, however, the effect decreased. To test whether the effect is blocked when NMDA binding sites are saturated with NMDA, high concentrations of NMDA were applied. To partially block Ca(2+) influx and prevent cells from deteriorating, the experiments were performed in the presence of either MK801 or kynurenate, two noncompetitive antagonists. Under such conditions, ifenprodil not only failed to potentiate NMDA currents, but consistently suppressed the current. When the same concentration of NMDA was applied in the presence of the competitive antagonist CGP37849, ifenprodil regained its ability to potentiate NMDA currents. Furthermore, the higher the concentration of CGP37849 the more the NMDA current was potentiated by ifenprodil. These results, combined with previous studies, suggest that the enhancing effect is due to an increase in NMDA receptor affinity and is specific for responses induced by low NMDA concentrations. As NMDA concentration increases, the affinity-enhancing effect decreases. Consequently, the channel-suppressing effect becomes more prominent.     

Evaluating patients with renal failure for renal artery stenosis with gadolinium-enhanced magnetic resonance angiography

The incidence and prevalence of end-stage renal disease (ESRD) continues to increase, especially in the elderly population. The role of renovascular disease in contributing to ESRD is still not well defined. The objective of this study was to determine the utility of gadolinium (Gd)-enhanced magnetic resonance angiography (MRA) in evaluating elderly patients with renal insufficiency for renal artery stenosis (RAS). A 7-month prospective study conducted in a tertiary referral center evaluated 40 consecutive patients with progressive renal insufficiency (18 men and 22 women; mean age, 70 +/- 5.6 [standard deviation] years) and high clinical suspicion for renovascular disease with Gd-enhanced MRA. Digital subtraction angiography (DSA) was obtained in only those patients with significant RAS detected by MRA. Twelve patients had significant RAS. Six of these patients had percutaneous transluminal renal angioplasty (PTRA), five patients had renal artery bypass surgery, and one patient had a stent placed after PTRA. Seventy-eight renal arteries were satisfactorily evaluated by MRA. Twenty-two renal arteries were evaluated by both MRA and DSA. Of the 12 significant stenoses detected by the MRA, 11 were confirmed by DSA and 1 was confirmed at the time of surgical revascularization. It is concluded that Gd-enhanced MRA is a useful test for the evaluation of RAS in patients with compromised renal function.     

Stress-induced plasma beta-endorphin immunoreactivity may predict postoperative morphine usage

The relationship between stress and human behavior is studied using general surgery as a stress paradigm. As indices of arousal, presurgery and surgery plasma beta-endorphin and cortisol immunoreactivity are assessed. Behavioral analysis is restricted to the measurement of total morphine usage during the first 24 postoperative hours under standard PRN (as needed) clinical orders. Individual patient morphine requirements vary widely (12-56 mg). Both presurgery and mean surgery plasma beta-endorphin levels significantly predict morphine requirement, and similar, although not so strong, correlations are found for cortisol. Patient age is also found to be negatively correlated with morphine requirement. When multiple regression analysis is used, the variables of plasma beta-endorphin and age predict 70% of the variance in individual morphine requirements.