Pathological Fractures of the Proximal Femur in Children and Adolescents Treated with LCP Paediatric Hip Plate.

PURPOSE OF THE STUDY Exploring the therapeutic potential of pathological fractures treatment of the proximal femur in childhood with LCP paediatric hip plate system according to the principles of AO. MATERIAL AND METHODS Six children with pathological fractures of the proximal femur and with an unicameral bone cyst have undergone surgery in our institution, in the period between June 2018 up until December 2020. All patients were young boys with a mean age of 11.83 ± 3.43 years. According to the classification of Delbet-Colonna, three of the fractures were Type IV - intertrochanteric fractures and three were Type III - basocervical fractures. ccording to the AO Trauma classification, one of the fractures was complete transtrochanteric multifragmentary (31-M/3.2.III), two were complete transtrochanteric simple (31-M/3.1.III), one was Complete basocervical multifragmentary (31-M/3.2.II) and two were complete basicervical simple (31-M/3.1.II). All patients have undergone open reposition and osteosynthesis with a 130° LCP pediatric hip plate system (DePuy Synthes Pediatric LCP Plate System). In four of the patients, one or two of the proximal locking screws pass through the growth plate, to ensure more stability. The anatomical correction of the proximal femur has been measured through the cervico-diaphyseal angle, consolidation of the fracture, the spontaneous reparation of the cyst according to the Capanna classification and cystic index, presence of avascular necrosis of the epiphysis, shortening of the extremity, and functional grading by the Musculoskeletal Tumor Society (MSTS) staging system. The Mann-Whitney (Wilcoxon W) test was used for data processing. RESULTS The mean timing of the follow-up after the surgery was 22 months (range 6-32). A radiographically supported consolidation of the fracture has occurred at an average timing of 4.8 months (range 3-6) in all patients. There is no clinical or radiological evidence of postoperative avascular necrosis in any of the patients. According to the classification of Capanna, in five of the six patients a spontaneous reparation of the cyst has occurred. In one of the cases, the reparation is classified as grade II with a pathological cystic index of 2.27. A postoperative correction of the varus fracture deformity of the proximal femur has been achieved in all children. The cervical-diaphysary angle of 112.50° preoperatively has been corrected to 137.17° (p=0.002). The achieved correction is lasting and the average value of the CDS at the final follow-up is 138.17° (p=0.794). Intraoperative correction, statistically equal to the CDA of the healthy side (p=0.942) is achieved with this operative technique. Data from the MSTS show functional correction on the third postoperative month with 38.33% of the norm (p=0.002) and 85% on the final follow-up (p=0.002). A contralateral distal femoral surgical epiphysiodesis by the method of Métaizeau has been used for the correction of the difference in the length of the extremities (with an average of 2.9 cm). CONCLUSIONS Osteosynthesis with an LCP paediatric hip plate system gives the opportunity for anatomical correction of the proximal femur with a low risk of avascular necrosis and achieving optimal functional results in pathological basocervical and intertrochanteric fractures in childhood. The use of 5mm plates and penetration of the proximal screw through the growth plate holds an increased risk of growth disruption. Key words: LCP paediatric hip plate system, pathological fracture, unicameral bone cysts, proximal femur.

Memory effects of the Ca2+ and 5-HT antagonists dotarizine and flunarizine.

In experiments on Wistar and Long Evans rats, using behavioral methods for passive (step-down and step-through) and active (shuttle-box two-way avoidance with punishment reinforcement) the newly synthesized diphenyl-methyl-piperazine derivative with Ca2+ and 5-HT antagonistic action dotarizine (DOT) administered repeatedly at oral doses of 50 and 10 mg/kg in some cases improve memory process. Under the same experimental conditions the chemically related to dotarizine Ca2+ antagonist flunarizine significantly facilitated retention. In old (Long Evans and Wistar) rats DOT in large dose decreases values of learning criterion. Probably this is a manifestation of the inherent to drugs with nootropic action "therapeutic window". Earlier investigations of the same and other authors suggest the participation of serotonergic neurotransmission in the mechanism of the memory effects of the drug DOT.

Behavioral effects of the cyclic cholecystokinin peptide analogue JMV-320.

The in vivo effects of JMV-320 (a highly selective CCKB receptor ligand) and of CCK-4 on exploratory activity and memory in rats were compared. JMV-320 and CCK-4 did not modulate exploratory activity in an open field test but decreased it in an elevated plus-maze. CCK-4 (50 micrograms/kg) impaired passive avoidance response 3 h after training and JMV-320 (1 and 10 micrograms/kg) decreased active avoidance response 24 h after training. The behavioral effects of JMV-320 resemble the effects of CCK-4 and suggest that in vivo JMV-320 acts as a CCKB receptor agonist.

Participation of different 5-HT receptors in the memory process in rats and its modulation by the serotonin depletor p-chlorophenylalanine.

The memory effects of agonists and antagonists of some serotonin (5-HT) receptor subtypes were examined in experiments on rats using an active avoidance method (shuttle-box). The 5-HT receptor antagonists NAN 190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) improved some indices for memory; the 5-HT2 and 5-HT3 receptor antagonists ritanserin (1 mg/kg i.p.) and ondansetron (0.1 mg/kg i.p.) exerted a favourable effect on the mastering of active avoidance performance. The tryptophan hydroxylase inhibitor para-chlorophenylalanine (300 mg/kg i.p.) alone produced no significant changes in the indices for retention of learned behaviour but in combination with the 5-HT-receptor agonists and antagonists influenced some of their effects. The results obtained show different participation of 5-HT1A, 5-HT2 and 5-HT3 receptors in the mechanisms of the memory process; the nature of this involvement is modulated by the brain level of serotonin.

Behavioural effects of two cholecystokinin analogues: JMV 236 and JMV 179.

The behavioural effects of two cholecystokinin analogues Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 (JMV 236), a potent CCK agonist, and Boc-Tyr(SO3H)-Nle-Gly-DTrp-Nle-Asp-2-Phenylethylester (JMV 179), a CCK antagonist were studied. JMV 236 (3.125, 12.5 and 50 micrograms/kg i.p.) dose-dependently decreased the exploratory activity of rats, the effect being significant for horizontal activity (ambulation) at doses of 12.5 and 50 micrograms/kg and for vertical activity (rearing) at a dose of 50 micrograms/kg. JMV 179 (3.125, 12.5 and 50 micrograms/kg i.p.) did not change the horizontal activity but dose-dependently decreased the vertical activity, the effect being significant at a dose of 50 micrograms/kg. JMV 236 administered immediately after training significantly facilitated short-term memory in passive avoidance situation but only tended to increase the mean latency upon retention testing on the 7th day. JMV 179 tended to increase the latency of the passive avoidance response upon retention testing at the 24th hour but not on the 7th day after training.

Effects of agonists and antagonists of some serotonin-receptor subtypes on memory and their modulation by the 5-HT-uptake inhibitor fluoxetine.

The memory effects of agonists and antagonists of some serotonin (5-HT)-receptor subtypes were studied in experiments on rats using the method for passive avoidance with punishment reinforcement (step-down). The 5-HT1A-receptor agonist buspirone (1 mg/kg i.p.) elicited behavioural responses which suggested the lack of pronounced effect on learning and retention; the 5-HT1A-receptor antagonists NAN-190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls. The 5-HT2-receptor antagonist ritanserin (1 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls, while the 5-HT3-receptor antagonist ondansetron (0.1 mg/kg i.p.) improved it. The 5-HT1/5-HT2-receptor antagonist dotarizine (50 mg/kg orally), characterized by a calcium-antagonistic action, too, exerted some facilitating effect on learning. Most of the effects of the 5-HT-receptor agonists and antagonists were changed when the 5-HT concentration in the synaptic region was increased by the 5-HT-uptake inhibitor fluoxetine (20 mg/kg orally). The results suggest different participation of 5-HT1A-, 5-HT2- and 5-HT3-receptors in the mechanisms of memory process and its modulation by the serotonin level in the cerebral serotonergic synapses.

Effects of cytidine diphosphate choline on rats with memory deficits.

The effects of cytidine diphosphate choline (CDP-choline, CAS 987-78-0) on learning and memory in rats with memory deficits were examined using behavioral methods of active avoidance with punishment reinforcement (shuttle-box), passive avoidance with punishment reinforcement (step-through and step-down), and active avoidance with positive (alimentary) reinforcement (staircase-maze). In the majority of experiments CDP-choline was applied orally at doses of 10-50 or 100 mg/kg daily for 7 days before the training session. The experiments were carried out on young-adult (aged 5 months) and old (aged 22 months) rats and on rats with a low capability for retention of learned behavior. Memory deficits were induced by the muscarinic cholinoceptor antagonist scopolamine (in young and old rats and mice), by the alpha 2-adrenoceptor agonist clonidine, by electroconvulsive shock, and by hypoxy. Memory deficits were also induced in rats offspring of dams that had been exposed to alcohol during pregnancy and lactation. The results suggest that CDP-choline acts as a memory-enhancing drug and that its effect is particularly pronounced in animals with memory deficits.

Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (PHL-00701).

In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs. The favorable effects on learning and memory of the combination of G115 plus GK501 and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice.

Effect of CDP-choline on learning and memory processes in rodents.

The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP-choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels.

Age-related differences in memory and in the memory effects of nootropic drugs.

In experiments of 2-, 5-, 10- and 22-month old rats, using active avoidance with punishment reinforcement (maze and shuttle-box) and passive avoidance (step-down), we found that acquisition and retention in aged rats were impaired significantly or only as a trend. The nootropics adafenoxate, meclofenoxate, citicholine, aniracetam and the standardized ginseng extract administered orally for 7 to 10 days usually facilitated learning and improved memory in the rats of all ages. By some of the indices used the drugs gave more pronounced favourable effects in old rats, while by others better effects were observed in young or adult rats. The results demonstrate significant age-related differences in learning and memory in rats and in the effects of nootropic drugs on these processes.

Significance of the cerebral dopaminergic neurotransmission for the individual differences in learning and memory (experiments on rats).

Using the step-down method for passive avoidance with punishment electroshock reinforcement, the experimental rats were divided according to their individual differences in the capacity for learning and retention into two groups: good learners (GL) and poor learners (PL). Stereotypy and catalepsy methods were used in order to clarify the role of the central dopaminergic (DA-ergic) transmitter mechanisms for the individual differences. Stereotypic motor behaviour was induced by applying the following DA-ergic agonists: apomorphine (2 mg/kg. i.p.), amphetamine (6 mg/kg, s.c.) and elymoklavine (2 mg/kg, i.p.). The stereotypic behaviour was recorded on a 5-point scale. A set of catalepsy tests was used to determine the cataleptic effect of the DA-ergic antagonist haloperidol (1 mg/kg, i.p.). Our experimental results showed that the intensity and duration of the stereotypy caused by the three agents were significantly increased in GL compared with PL. Catalepsy in the PL group appeared later than in the GL group, and its total duration was shorter. The data obtained suggest that in the GL group there is a marked tendency towards a higher level of sensitivity of the brain dopamine receptors, compared with the PL group.

Age-determined changes in the effects of a newly synthetized cholinesterase inhibitor on exploratory behavior, memory and striatal cholinesterase activity in rats.

The newly synthetized cholinesterase inhibitor C-8 (a structural analogue of physostigmine) at a dose of 4 mg.kg-1 exerted no inhibitory effect on the spontaneous locomotor activity in 2-, 10- and 22-month old male Wistar rats. Upon open field test, C-8 facilitated the process of habituation in the rats of all three groups. In a passive avoidance situation (step-down and step-through) C-8 had a favorable effect on the memory of 22-month old rats mainly. C-8 inhibited the cholinesterase activity in the striatum of 2-month old rats by 29%, in 10-month old rats by 73%, and in 22-month old rats by 30%.

Individually-determined differences in the effects of psychotropic drugs on memory (experiments on rats).

Using the methods for "staircase-maze" training with positive (alimentary) reinforcement and "steps down" passive avoidance with punishment (electroshock) reinforcement, we divided the experimental animals into three groups: "good", "intermediate", and "poor" learners. In the course of seven days the animals of the three groups were treated with five substances and were then tested for retention with both methods. Amphetamine at single doses of 0.1 and 0.5 mg/kg was injected s. c. 30 min before the retention test given on the 7th day after the end of training. The other four drugs were administered twice daily throughout the period between the end of training and retention testing (seven days). Adafenoxate was applied at a dose of 10 mg/kg, piracetam at doses of 50, 150, and 300 mg/kg, and aniracetam at doses of 50 and 150 mg/kg--all the three drugs were administered orally; citicholine was injected at doses of 10 and 50 mg/kg i. p. The effects of the substances tested significantly differed depending on the animal's belonging to one or another group. Furthermore, depending on the retention test, the drug tested and the dose used, we observed differences in the effects not only in the different groups but also in one and the same group. Not taking into account the individual capabilities of experimental animals to acquire a retention task might lead to an incorrect characterization of such an important property of psychotropic drugs as their effect on memory process.