Immunosuppression in renal transplantation: Long-term clinical trial of a double versus triple therapy regimen

Summary: Sixty-nine renal allograft recipients were randomized to two immunosuppressive regimens: 35 patients received cyclosporine A and prednisolone (PC) while 34 patients received low dose cyclosporine A, prednisolone and short term azathioprine (PCA). the data of 66 patients (34 in PC and 32 in PCA groups) were analysed. the median follow-up periods were 62 months for the PC group and 60 months for the PCA group. There was no difference in graft survival between the two groups but five patients died in the PC group compared to none in the PCA group (graft survival: 88 vs 90% at 1 year and 82 vs 82% at 5 years, P = not significant at any time point; patient survival: 90 vs 100% at 1 year and 88 vs 100% at 5 years, P = 0.05 at 5 years). There was a trend for patients in the PCA group to develop earlier and more frequent rejections (not significant; P = 0.106 and P = 0.062, respectively). There were also more episodes of acute cyclosporine A nephrotoxicity and cytomegalovirus (CMV) infection in the PC group. the mean serum creatinine at 5 years was significantly higher in the PCA group when compared to the PC group (179.8 ± 76.5 μmol/L vs 154.7 ± 41.0 μmol/L; P =0.05). We found that both therapeutic regimens were effective in preventing renal allograft rejections. However, double therapy was associated with higher patient mortality secondary to infection. Patients on triple therapy, on the other hand, were more prone to develop rejections in the early post-transplant period and were associated with less favourable renal function in the long run.     

Taste aversions conditioned with gamma radiation: Attenuation by area postrema lesions in rats

The role of the area postrema in radiation induced taste aversions in rats was examined. One group of rats received lesions of the area postrema, another group was given sham lesions and a third group received no surgery. These three groups of rats were then given one pairing of 1 h access to a novel 0.15% sodium saccharin solution followed immediately with exposure to 200 rad gamma radiation. A fourth group of rats with area postrema lesions was given 1 h access to saccharin followed by a sham irradiation procedure. Four days later all groups were given daily two bottle preference tests (saccharin vs water) on 5 consecutive days. The groups with sham lesions or no surgery displayed a strong aversion to saccharin on all 5 test days. The two area postrema lesioned groups displayed a moderate and increasing preference for saccharin over the 5 day test period. The lesioned group given radiation treatment showed a weak but significant aversion (P < 0.05) to saccharin on the first test day, when compared to the lesioned rats not given radiation treatment. Thus, lesions of the area postrema strongly attenuated the radiation induced taste aversions, but did not completely abolish them.     

Conditioned taste aversions induced by 1–5-hydroxytryptophan are mediated by the area postrema

1. Previous studies have shown that injections of 5-HTP can induce conditioned taste aversions when paired with a novel taste.

2. Adult male albino rats received either lesions of the area postrema or were subjected to a sham lesion procedure.

3. All rats were adjusted to a 23 hr/day water deprivation schedule and on the conditioning day were given a 0.15% saccharin solution for hr. After drinking the saccharin fluid 9 area postrema lesioned and 10 sham lesioned rats were injected i.p. with 25 mg/kg 1–5-hydroxytryptophan. Similarly 10 area postrema lesioned and 6 sham lesioned rats were injected with the vehicle solution.

4. A two-bottle choice test between the saccharin solution and water was given to all animals on the third and fourth days after the conditioning day.

5. The sham lesioned rats injected with the 1–5-hydroxytryptophan exhibited a strong aversion to the saccharin taste whereas the vehicle injected sham lesioned rats showed an equal preference for the two fluids. The difference in group mean saccharin preference ratio was significant (p < .01).

6. Both area postrema lesioned groups exhibited saccharin preference ratios that were comparable to and not significantly different from the sham lesioned animals injected with the vehicle solution.

7. These results show that an intact area postrema is necessary for induction of conditioned taste aversions with 1–5-hydroxytryptophan.     

Sodium arsanilate-induced vestibular dysfunction in rats: effects on open-field behavior and spontaneous activity in the automated digiscan monitoring system

Vestibular dysfunction was chemically induced in Long-Evans rats by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). Following a one-week recovery period the rats were behaviorally assayed for integrity of the labyrinthine systems. All subjects were tested for presence of the air-righting reflex, the contact-righting reflex (by lightly holding a sheet of Plexiglas against the soles of the rat's feet), and body rotation-induced nystagmus. All animals were then tested for their ability to remain on a small (15 x 15 cm) platform. Next, the subjects were given two 10-min open-field tests during which ambulation, rearing, grooming, and defecation responses were recorded. Four to five weeks later all rats were tested twice (60 min per session) in the automated Digiscan Activity Monitor which provides a multivariate assessment of spontaneous motor activity. The rats with vestibular dysfunction (Group VNX) took significantly less time to fall off the platform (p less than 0.01). They also exhibited significantly more open-field ambulation but fewer rearing responses (ps less than 0.01). An examination of group correlation coefficients for open-field variables and the platform test scores revealed some interesting group differences (ps less than 0.05). In the Digiscan tests the atoxyl-treated rats exhibited fewer number of horizontal movements, but increased speed for these movements (ps less than 0.05). Vertical movements did not differ significantly in incidence, but these movements were greatly reduced in duration (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exposure to rotating magnetic fields alters morphine-induced behavioral responses in two strains of mice

An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced the day-time analgesic and locomotory effects of morphine (10 mg/kg) in CF-1 and C-57BL strains of mice, respectively. Exposure to lower intensity 60 Hz magnetic fields (0.-1.0 G) had no effect on analgesia induced by morphine. The reduction in responsiveness to morphine after exposure to the greater intensity rotating field was not evident 24 hr later. No changes were seen in the latencies of basal thermal responses or levels of activity of saline-treated mice exposed to the magnetic stimuli.     

Influence of the estrous cycle on tolerance development to LPS-induced sickness behaviors in rats

The relations between the estrous cycle, inflammatory responses and the development of tolerance to endotoxin were examined. Female Long-Evans rats were injected intraperitoneally with lipopolysaccharide (LPS; 200 microg/kg) or saline vehicle at 08:00h on either diestrus (D) or proestrus (P). Ninety-five minutes after injection locomotor activity was assessed in an automated non-novel open-field for 20 min. To assess tolerance development to LPS, rats were re-injected at the next identical stage (i.e. 4 days later; groups: DD, PP) or at the alternate stage (i.e. 6 days later; groups: DP, PD) of the estrous cycle and locomotor activity was again assessed. On Test Day 1 all groups injected with LPS exhibited similar significant activity decrements, regardless of the stage of the estrous cycle. However, on Test Day 2 rats which received both injections of LPS during proestrus (PP) showed no signs of tolerance development, whereas rats in all other groups were tolerant to LPS. In a follow up study, the time between injections was extended to 8 days. Still the animals injected both times at proestrus showed no signs of tolerance to LPS after the second injection. Thus, the stages of the estrous cycle both at the time of initial exposure and of re-exposure appear critical in the formation of behavioral tolerance to LPS in rats.     

Quinpirole-induced behavioral sensitization is enhanced by prior scheduled exposure to sucrose: A multi-variable examination of locomotor activity

Sensitization of dopaminergic neural reward circuits has been hypothesized to be involved in the development of drug addiction. Highly palatable foods activate these same brain areas, specifically the nucleus accumbens. In this study, the effects of a highly palatable food (sucrose) on these circuits were investigated using the dopamine D(2)/D(3) receptor agonist quinpirole. Male Long-Evans rats received 30 min daily access to 0.3 M sucrose solution or water over nine consecutive days, followed by nine daily injections of quinpirole (0.5 mg/kg, s.c.) or saline. Locomotor activity was assessed using an automated open-field system. Locomotor sensitization developed, as quinpirole-treated rats traveled significantly more, and exhibited a greater number of movements than saline controls. A characteristic pattern of an initial suppression of locomotor activity, followed by excitation of activity was observed in quinpirole-treated rats. Pre-exposure to sucrose attenuated the initial suppression of activity, and facilitated excitation of activity. Rats that were pre-exposed to sucrose exhibited a reduced suppression of activity as compared to rats pre-exposed to water. Rats receiving sucrose and quinpirole also displayed a significantly greater enhancement of locomotor activity as compared to rats receiving water and quinpirole. These results support the hypothesis that highly palatable foods can alter the same neural reward circuits as drugs of abuse, and may facilitate sensitization-related addiction. This may aid in further understanding the neural basis of eating disorders.     

First experience with robotic pancreatoduodenectomy in Singapore

INTRODUCTIONRecent studies reported that laparoscopic pancreatoduodenectomy (LPD) is associated with superior perioperative outcomes compared to the open approach. However, concerns have been raised about the safety of LPD, especially during the learning phase. Robotic pancreatoduodenectomy (RPD) has been reported to be associated with a shorter learning curve compared to LPD. We herein present our initial experience with RPD.METHODSA retrospective review of a single-institution prospective robotic hepatopancreaticobiliary (HPB) surgery database of 70 patients identified seven consecutive RPDs performed by a single surgeon in 2016–2017. These were matched at a 1:2 ratio with 14 open pancreatoduodenectomies (OPDs) selected from 77 consecutive pancreatoduodenectomies performed by the same surgeon between 2011 and 2017.RESULTSSeven patients underwent RPD, of which five were hybrid procedures with open reconstruction. There were no open conversions. Median operative time was 710.0 (range 560.0–930.0) minutes. Two major morbidities (> Grade 2) occurred: one gastrojejunostomy bleed requiring endoscopic haemostasis and one delayed gastric emptying requiring feeding tube placement. There were no pancreatic fistulas, reoperations or 90-day/in-hospital mortalities in the RPD group. Comparison between RPD and OPD demonstrated that RPD was associated with a significantly longer operative time. Compared to open surgery, there was no significant difference in estimated blood loss, blood transfusion, postoperative stay, pancreatic fistula rates, morbidity and mortality rates, R0 resection rates, and lymph node harvest rates.CONCLUSIONOur initial experience demonstrates that RPD is feasible and safe in selected patients. It can be safely adopted without any compromise in patient outcomes compared to the open approach.