Pain and anxiety associated with Computer-Controlled Local Anaesthesia: systematic review and meta-analysis of cross-over studies.

AIM: This review focuses on Computer-Controlled Local Anaesthesia Delivery systems (CCLAD), in comparison with conventional carpule anaesthesia in means of pain and anxiety. METHODS: Medline, Embase, Web of Science and Cochrane Database for Systematic Reviews were searched up to August 2018. Only cross-over split-mouth design studies aimed to clinically compare CCLAD with a conventional carpule anaesthesia are included. Data about pain and anxiety associated with anaesthesia were sought. The authors performed meta-analysis where appropriate. RESULTS: A total of 20 studies are included in the systematic review (n = 973 subjects). Quantitative synthesis (conducted on VAS scores from 8 studies) shows that pain intensity is over 9 points lower in CCLAD than in conventional anaesthesia on a scale from 0 to 100 (95% confidence interval, ?12.90 to ?5,53; P<.001). The systematic review showed no differences between the two techniques according to the physiological parameters of pain (heart rate or blood pressure), and the data about anxiety are inconsistent. CONCLUSION: CCLAD results in significantly slightly less pain perception with respect to conventional injection and is a promising device to help patients. The literature needs to be expanded, mostly regarding anxiety.

White matter reduced streamline coherence in young men with autism and mental retardation.

BACKGROUND AND PURPOSE: It has been proposed that white matter alterations might play a role in autistic disorders; however, published data are mainly limited to high-functioning autism. The goal of this study was to apply diffusion tensor imaging (DTI) and fiber tractography (FT) to study white matter in low-functioning autism and the relationship between white matter and cognitive impairment. METHODS: Ten low-functioning males with autism (mean age: 19.7 +/- 2.83 years) and 10 age-matched healthy males (mean age: 19.9 +/- 2.64 years) underwent DTI-MRI scanning. fractional anisotropy (FA) maps were analyzed with whole brain voxel-wise and tract-of-interest statistics. Using FT algorithms, white matter tracts connecting the orbitofrontal cortex (OFC) with other brain regions were identified and compared between the two groups. FA mean values of the autistic group were correlated with intelligence quotient (IQ) scores. RESULTS: Low-functioning autistic subjects showed a reduced tract volume and lower mean FA values in the left OFC network compared with controls. In the autistic group, lower FA values were associated with lower IQ scores. CONCLUSIONS: We showed evidence of OFC white matter network abnormalities in low-functioning autistic individuals. Our results point to a relationship between the severity of the intellectual impairment and the extent of white matter alterations.

Comparison of epidural, continuous femoral block and intraarticular analgesia after anterior cruciate ligament reconstruction.

BACKGROUND: The purpose of this study was to compare three locoregional techniques of pain management after arthroscopic anterior cruciate ligament reconstruction (ACLR). METHODS: Sixty ASA I-II subjects were enrolled after obtaining written informed consent. Patients were randomly allocated to three groups of 20 subjects. The first group (EPI) received epidural ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. Patients in the second group (CFB) were given a continuous infusion of the same analgesic mixture through a femoral catheter. The third group (IA) received a continuous intraarticular infusion of ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. All subjects were allowed PCA boluses of 5 ml of local anesthetic. Analgesia was assessed for 36 h after the end of surgery by means of a visual analog scale (VAS) and a verbal scale (VS), as well as the number of PCA boluses administered and the amount of supplementary i.v. ketorolac, if given. RESULTS: The VAS and VS scores were significantly higher in group IA during the 24 h following surgery. Ketorolac requirement was higher in group IA throughout the postoperative observation. Adverse effects were similar in all groups except for urinary retention, which was significantly more frequent in group EPI. CONCLUSIONS: We conclude that either epidural or continuous femoral nerve block provide adequate pain relief in patients who undergo ACLR, whereas intraarticular analgesia seems unable to cope satisfactorily with the analgesic requirements of this surgical procedure.

Effects of cholecystokinin octapeptide on the hypothalamic-pituitary-adrenal axis function and on vasopressin, prolactin and growth hormone release in humans.

Cholecystokinin (CCK), a gastrointestinal (GI) hormone, is also present in structures of the central nervous system such as cortex, hippocampus, amygdala, olfactory tubercle and in regions involved in the regulation of the pituitary function. Although a number of studies have evaluated the effects of CCK on hypothalamic-pituitary-adrenal (HPA) axis function and on arginine vasopressin (AVP), prolactin (PRL) and growth hormone (GH) plasma levels in the laboratory animal, its role in humans has not been explored. Hence, we examined the effects of the exogenous administration of this GI hormone on corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, AVP, PRL and GH plasma levels in humans. To accomplish this, graded doses (0, 50, 140 and 420 ng/kg) of sulfated CCK octapeptide (CCK-8), the full biologically active peptide, were infused intravenously to healthy men in 30 min. Blood samples were collected 30 min and immediately before the infusion was started (baseline) and 15, 30, 45, 60 and 90 min thereafter. CRH, ACTH, and AVP were extracted from plasma proteins using cartridges of SepPak C18. These hormones and cortisol were measured by radioimmunoassay whereas PRL and GH were measured by immunoradiometric assay. CCK-8 increased plasma ACTH and cortisol levels only at the dose of 420 ng/kg, whereas it had no detectable effect on plasma CRH levels. It increased also plasma AVP levels at the doses of 140 and 420 ng/kg. However, this effect reached the statistical significance only at the highest dose tested. CCK-8 stimulated PRL and GH release in a dose-dependent fashion. The lowest stimulatory dose was 140 ng/kg for both hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

lntra- and Inter-Individual Variability in Growth Hormone Responses to Growth Hormone-Releasing Hormone*.

Abstract Normal subjects show a wide range of growth hormone (GH) responses to growth hormone-releasing hormone (GHRH) stimulation, but it is uncertain whether this variability reflects differences among individuals or whether it would also be observed on repeated tests of the same subject. To clarify this, we tested nine normal men repeatedly with iv bolus doses of 1 mug/kg GHRH(1-44)NH(2). Most subjects showed wide variations in their GH responses on repeated testing, and the intra-individual variability was nearly as great as the inter-individual variability in responses, accounting for about two-thirds of the overall variance. A minority of subjects had lower and less variable responses. Ultradian fluctuations in hypothalamic somatostatin secretion may account for this marked intra-individual variability.

Dynamics of plasma gonadotropin and sex steroid release in polycystic ovarian disease after pituitary-ovarian inhibition with an analog of gonadotropin-releasing hormone.

To assess the dynamics of the suppression and recovery of plasma gonadotropins and sex steroids during and after inhibition of pituitary-ovarian function by a long-acting agonist GnRH-analog (GnRH-A), eight patients with polycystic ovarian disease were treated with 12 micrograms/kg X day GnRH-A for 56 consecutive days. In response to GnRH-A, these patients had a sharp and pronounced decline of their initially elevated immunoreactive LH and bioactive LH (bioLH) levels. Plasma immunoreactive FSH levels declined more rapidly than did bioLH, but the FSH decline was less sustained. Plasma testosterone, androstenedione, and estrone (E1) levels also declined during GnRH-A administration. The pattern of plasma androgen decrease resembled that of bioLH. There was a positive correlation between bioLH and the two androgens (r = 0.85; P less than 0.05, by Spearman's rank correlation, for both hormones). Cessation of GnRH-A administration was followed by prompt progressive increases in gonadotropin and androgen concentrations to pretreatment values. FSH recovered faster than bioLH. BioLH plasma concentrations reached pretreatment values by day 28. The recovery of plasma androstenedione and testosterone levels correlated positively with that of bioLH. Although plasma E1 levels were higher during the recovery period than during treatment, they never reached the concentrations found during the basal period, whereas estradiol concentrations were slightly but not significantly higher than those in the basal period. As a consequence, the E1 to estradiol ratio, very high in the basal period, approximated unity during recovery. These data indicate that hyperandrogenism in polycystic ovarian disease is gonadotropin dependent and accompanied by a relative abundance of LH bioactivity basally and during GnRH-A administration. Thus, the relative increase in bioLH secretion appears to be independent of the rate of gonadotropin secretion and the circulating sex steroid concentrations.

Failure of GnRH analogue to inhibit serum concentrations of testosterone and 17 alpha-hydroxyprogesterone in hCG-substituted hypogonadotropic hypogonadism.

Gonadotropin-releasing hormone analogues (GnRH-A) induce inhibition of testicular function and reduction of serum testosterone (T) in man, but the mechanism involved is still debatable. To elucidate it we studied six patients with hypogonadotropic hypogonadism (HH) in chronic substitution with hCG for correction of androgen deficiency symptoms, and evaluated the effect of addition of GnRH-A to the hCG therapy on plasma levels of T and 17 alpha-hydroxyprogesterone (17 OHP). All patients were treated with 1000 U of hCG in every 3rd day for 24 weeks. After 8 weeks of this regimen, GnRH-A, Buserelin (D-Ser-TBU-EA-LHRH), 200 micrograms per day sc, was added and given for 8 weeks. After cessation of analogue administration patients were followed for 8 further weeks. The levels of the two steroids did not differ markedly in the pre- and post-GnRH-A period. GnRH-A given for two months did not lower T or 17 OHP levels as in eugonadal men after similar treatment. The median T concentrations during GnRH-A tended to be increased, with plasma values higher (P less than 0.025) than the peak values observed during hCG alone. Since administration of Buserelin did not inhibit hCG-sustained steroid levels in these HH patients, it is conceivable that GnRH-A may have lacked a direct inhibitory gonadal effect in such experimental conditions.

Effect of gonadotrophin-releasing hormone analogue (GnRH-A) administration on serum gonadotrophin and steroid levels in patients with polycystic ovarian disease.

A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 micrograms was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P less than 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4, 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P less than 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P less than 0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.

Down-regulation of prolactin secretion in men during continuous thyrotropin-releasing hormone infusion: evidence for induction of pituitary desensitization by continuous TRH administration.

TRH was administered as a 5-h constant rate iv infusion (5 micrograms/min) to seven healthy adult men. Serum samples were collected at regular intervals for measurement of PRL, TSH, and T3. Serum levels of PRL during TRH infusion increased sharply to maximum level by 40 min, and then, despite continued TRH stimulation, PRL levels declined gradually to a plateau value after 100 min. No further rise in serum PRL was observed when a bolus of 200 micrograms TRH was administered to three subjects after 240 min of infusion. Conversely, an iv bolus of sulpiride (25 mg), a dopaminergic antagonist, given to four subjects after 240 min, brought about a marked increase in serum PRL values above the plateau level. These results are consistent with the interpretation that down-regulation in PRL secretion which follows the initial peak of response most likely represents pituitary desensitization to TRH. During the infusion serum TSH increases in two phases. A first phase of secretion was observed by 40 min followed by a plateau, with a second phase of increase occurring between 80-180 min.