PIT

Comparison of the diagnostic ability of blue laser imaging magnification versus pit pattern analysis for colorectal polyps.[Pubmed:28367494]

Endosc Int Open. 2017 Apr;5(4):E224-E231.

Background and study aims There have been few evaluations of the diagnostic ability of new narrow band light observation blue laser imaging (BLI). The present prospective study compared the diagnostic ability of BLI magnification and PIT pattern analysis for colorectal polyps. Patients and methods We collected lesions prospectively, and the analysis of images was made by two endoscopists, retrospectively. A total of 799 colorectal polyps were examined by BLI magnification and PIT pattern analysis at Nagoya University HosPITal. The Hiroshima narrow-band imaging classification was used for BLI. Differentiation of neoplastic from non-neoplastic lesions and diagnosis of deeply invasive submucosal cancer (dSM) were compared between BLI magnification and PIT pattern analysis. Type C2 in the Hiroshima classification was evaluated separately, because application of this category as an index of the depth of cancer invasion was considered difficult. Results We analyzed 748 colorectal polyps, excluding 51 polyps that were inflammatory polyps, sessile serrated adenoma/polyps, serrated adenomas, advanced colorectal cancers, or other lesions. The accuracy of differential diagnosis between neoplastic and non-neoplastic lesions was 98.4 % using BLI magnification and 98.7 % with PIT pattern analysis. In addition, the diagnostic accuracy of BLI magnification and PIT pattern analysis for dSM for cancer was 89.5 % and 92.1 %, respectively. When type C2 lesions were excluded, the diagnostic accuracy of BLI for dSM was 95.9 %. The 18 type C2 lesions comprised 1 adenoma, 9 intramucosal or slightly invasive submucosal cancers, and 8 dSM. PIT pattern analysis allowed accurate diagnosis of the depth of invasion in 13 lesions (72.2 %). Conclusions Most colorectal polyps could be diagnosed accurately by BLI magnification without PIT pattern analysis, but we should add PIT pattern analysis for type C2 lesions in the Hiroshima classification.

Reducing Operating Room Turnover Time for Robotic Surgery Using a Motor Racing Pit Stop Model.[Pubmed:28357497]

World J Surg. 2017 Aug;41(8):1943-1949.

BACKGROUND: Operating room (OR) turnover time, time taken between one patient leaving the OR and the next entering, is an important determinant of OR utilization, a key value metric for hosPITal administrators. Surgical robots have increased the complexity and number of tasks required during an OR turnover, resulting in highly variable OR turnover times. We sought to streamline the turnover process and decrease robotic OR turnover times and increase efficiency. METHODS: Direct observation of 45 pre-intervention robotic OR turnovers was performed. Following a previously successful model for handoffs, we employed concepts from motor racing PIT stops, including briefings, leadership, role definition, task allocation and task sequencing. Turnover task cards for staff were developed, and card assignments were distributed for each turnover. Forty-one cases were observed post-intervention. RESULTS: Average total OR turnover time was 99.2 min (95% CI 88.0-110.3) pre-intervention and 53.2 min (95% CI 48.0-58.5) at 3 months post-intervention. Average room ready time from when the patient exited the OR until the surgical technician was ready to receive the next patient was 42.2 min (95% CI 36.7-47.7) before the intervention, which reduced to 27.2 min at 3 months (95% CI 24.7-29.7) post-intervention (p < 0.0001). CONCLUSIONS: Role definition, task allocation and sequencing, combined with a visual cue for ease-of-use, create efficient, and sustainable approaches to decreasing robotic OR turnover times. Broader system changes are needed to caPITalize on that result. PIT stop and other high-risk industry models may inform approaches to the management of tasks and teams.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.[Pubmed:28356564]

J Hum Genet. 2017 Aug;62(8):755-762.

PITuitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined PITuitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of PITuitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Prominent sympathetic purinergic vasoconstriction in the rabbit splenic artery: potentiation by 2,2'-pyridylisatogen tosylate.[Pubmed:9031760]

Br J Pharmacol. 1997 Feb;120(3):530-6.

1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 microM or guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced both neurogenic and myogenic responses. 2. Prazosin (1 microM) did not significantly affect vascular contractions to electrical stimulation. Desensitization of P2X-purinoceptors with alpha, beta-methylene ATP (alpha, beta-meATP, 3 microM) abolished the contractions to stimulation at 2-8 Hz and inhibited more than 80% of the vascular response at 16 Hz, but it did not significantly change the responses at 32 Hz. Contractile responses at 32 Hz were inhibited by a combination of prazosin and alpha, beta-meATP. Effects of pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid tetrasodium salt (a selective P2X-purinoceptor antagonist) and suramin (a competitive P2-purinoceptor antagonist) on the neurogenic responses were investigated in this study. 3. 2,2'-Pyridylisatogen tosylate (PIT, 0.3-3 microM) significantly potentiated the vasoconstrictions to electrical stimulation at 2-32 Hz in a concentration-dependent manner. Potentiated responses were restored to the control level 30 min after washing. Concentration-dependent response curves for noradrenaline (NA) or alpha, beta-meATP were not significantly changed by 3 microM PIT, and vasoconstriction by adenosine 5'-triphosphate (ATP, 300 microM) was unaffected by PIT. Coomassie brilliant blue-G (1 microM), which shares the potentiating effect on a recombinant P2Y-purinoceptor with PIT (King et al., 1996), did not inhibit or potentiate the purinergically-mediated component of the response to sympathetic nerve stimulation. The selective alpha 2-adrenoceptor antagonist yohimbine (1 microM) also potentiated the vascular responses to electrical stimulation. 4. The present results indicate that ATP evokes postjunctional contractile responses at low and high frequency electrical stimulation of sympathetic nerves supplying the rabbit splenic artery. PIT potentiates the responses to sympathetic (purinergic) nerve stimulation; this appears to be mainly via prejunctional rather than postjunctional actions.

Potentiation by 2,2'-pyridylisatogen tosylate of ATP-responses at a recombinant P2Y1 purinoceptor.[Pubmed:8882604]

Br J Pharmacol. 1996 Mar;117(6):1111-8.

1. 2,2'-Pyridylisatogen tosylate (PIT) has been reported to be an irreversible antagonist of responses to adenosine 5'-triphosphate (ATP) at metabotropic purinoceptors (of the P2Y family) in some smooth muscles. When a recombinant P2Y1 purinoceptor (derived from chick brain) is expressed in Xenopus oocytes, ATP and 2-methylthioATP (2-MeSATP) evoke calcium-activated chloride currents (ICl,Ca) in a concentration-dependent manner. The effects of PIT on these agonist responses were examined at this cloned P2Y purinoceptor. 2. PIT (0.1-100 microM) failed to stimulate P2Y1 purinoceptors directly but, over a narrow concentration range (0.1-3 microM), caused a time-dependent potentiation (2-5 fold) of responses to ATP. The potentiation of ATP-responses by PIT was not caused by inhibition of oocyte ecto-ATPase. At high concentrations (3-100 microM), PIT irreversibly inhibited responses to ATP with a IC50 value of 13 +/- 9 microM (pKB = 4.88 +/- 0.22; n = 3). PIT failed to potentiate inward currents evoked by 2-MeSATP and only inhibited the responses to this agonist in an irreversible manner. 3. Known P2 purinoceptor antagonists were tested for their ability to potentiate ATP-responses at the chick P2Y1 purinoceptor. Suramin (IC50 = 230 +/- 80 nM; n = 5) and Reactive blue-2 (IC50 = 580 +/- 130 nM; n = 6) reversibly inhibited but did not potentiate ATP-responses. Coomassie brilliant blue-G (0.1-3 microM) potentiated ATP-responses in three experiments, while higher concentrations (3-100 microM) irreversibly inhibited ATP-responses. The results indicated that potentiation and receptor antagonism were dissociable and not a feature common to all known P2 purinoceptor antagonists. 4. In radioligand binding assays, PIT showed a low affinity (pKi < 5) for a range of membrane receptors, including: alpha 1, alpha 2-adrenoceptors, 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, D1, D2, muscarinic, central benzodiazepine, H1, mu-opioid, dihydropyridine and batrachotoxin receptors. PIT showed some affinity (pKi = 5.3) for an adenosine (A1) receptor. 5. In guinea-pig isolated taenia caeci, PIT (12.5-50 microM) irreversibly antagonized relaxations to ATP (3-1000 microM); PIT also directly relaxed the smooth muscle and histamine was used to restore tone. Relaxations to nicotine (10-100 microM), evoked by stimulating intrinsic NANC nerves of taenia caeci preparations in the presence of hyoscine (0.3 microM) and guanethidine (17 microM), were not affected by PIT (50 microM, for 25-60 min). 6. These experiments indicate that PIT causes an irreversible antagonism of ATP receptors but, for recombinant chick P2Y1 purinoceptors, this effect is preceded by potentiation of ATP agonism. The initial potentiation by PIT (and by Coomassie brilliant blue-G) of ATP-responses raises the possibility of designing a new class of modulatory drugs to enhance purinergic transmission at metabotropic purinoceptors.

Antagonism of adenosine 5'-triphosphate-induced relaxation by 2-2'-pyridylisatogen in the taenia of guinea-pig caecum.[Pubmed:1148500]

Br J Pharmacol. 1975 Apr;53(4):575-83.

1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (greater than 10 min incubation with 50 muM PIT) and eventually became irreversible (greater than 50 muM PIT for greater than 30 minutes). The antagonism was specific for ATP, was not competitive, and was not dependent upon the relaxant effect. 3. The presence of either acetylcholine (0.05-1.0 muM) or carbachol (0.05-1.0 muM) increased the antagonistic effect of PIT (50 muM) approximately five-fold. 4. Following prolonged exposure, PIT (50 muM for 90 min) did not block the inhibitory effects of fiedl stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 muM). These results do not support the purinergic nerve hypothesis.