Estimation of99mTc-MAG3 clearance by single-sample methods and camera-based methods

We compared single-sample methods, proposed by Russell et al. and Bubeck et al., and camera-based methods in calculating 99mTc-MAG3 clearance, and determined camera-based methods that provide estimates comparable to those measured by the Russell method. Twenty-one patients underwent 99mTc-MAG3 renal scintigraphy, and clearance was measured by the Russell method and Bubeck method. Various renogram parameters were determined based on the slope of the renogram and area under the renogram, and correlated with the clearance measured by the Russell method. Camera-based clearance was calculated with the obtained regression equations and with equations determined previously using the Bubeck method as a standard. The Bubeck method provided lower measures than the Russell method in high renal function. Clearance measured by the Russell method was well correlated with renogram parameters, and clearance calculated with the obtained regression equation was comparable to that measured by the Russell method. When camera-based clearance was predicted with the previous equation, it was lower than the result obtained by the Russell method in high function. In conclusion, there are systematic differences in 99mTc-MAG3 clearance calculated by different methods. The camera-based methods obtained in this study appear to facilitate comparison of results obtained by the Russell method and camera-based method.     

Prophylactic IM small-dose phenylephrine blunts spinal anesthesia-induced hypotensive response during surgical repair of hip fracture in the elderly

In a double-blinded, placebo-controlled, randomized study, we evaluated the effect of prophylactic IM phenylephrine at doses of 1.5 and 3 mg on hyperbaric tetracaine spinal anesthesia-induced hypotension in 90 normotensive and hypertensive patients aged >65 yr undergoing surgery for hip fracture. Thirty normotensive patients received 1.5 or 3 mg of phenylephrine IM (N/P-1.5 and N/P-3.0 groups; n = 15 in each), whereas controls received saline (N/C group; n = 15), and 45 hypertensive patients were treated in a similar manner (H/P-1.5, H/P-3.0, and H/C groups; n = 15 in each). All groups had a peak sensory block height of T9, with a range of T8 to T10. The incidence of hypotension (>25% decrease in mean arterial blood pressure [MAP] from baseline) was significantly lower in the patients who received phenylephrine 1.5 or 3 mg than in the controls, both in the normotensive and hypertensive groups (P < 0.01). The N/P-3.0 and N/P-1.5 groups and the H/P-3.0 group had significantly lower percentage reductions in MAP (P < 0.05) and required significantly smaller doses of rescue IV ephedrine (P < 0.05) than did the N/C group or the H/C group. The H/P-1.5 group also required significantly less rescue IV ephedrine (P < 0.05), although it was not sufficient to significantly attenuate the percentage decrease in MAP compared with that in the H/C group. Bradycardia (heart rate <50 bpm) as an adverse effect after IM administration of phenylephrine was not observed in any of the groups. Hypertension (MAP >20% increase from baseline) after medication occurred in the N/P-3.0 and H/P-3.0 groups, but not in the N/P-1.5 and H/P-1.5 groups. We conclude that prophylactic IM injection of 1.5 mg of phenylephrine is a safe (defined as the inhibition of bradycardia and hypertension) and effective means of reducing the incidence of hypotension associated with spinal anesthesia in normotensive and hypertensive elderly patients. IMPLICATIONS: We evaluated the efficacy and safety of small-dose IM phenylephrine for prophylaxis against spinal anesthesia-induced hypotension in normotensive and hypertensive elderly patients. Phenylephrine 1.5 mg IM was effective for reducing the incidence of hypotension and avoided adverse effects.     

Different mechanisms of development and maintenance of experimental incision-induced hyperalgesia in human skin

BACKGROUND: To determine the mechanisms of postoperative pain, the effects of local anesthesia on development and maintenance of surgical incision-induced hyperalgesia were evaluated in a crossover, double-blinded, placebo-controlled human study using 17 subjects. METHODS: An experimental 4-mm-long incision through skin, fascia, and muscle was made in the volar forearm of each subject. In experiment 1, 1% lidocaine or saline in a volume of 0.2 ml was subcutaneously injected into the incision site pretraumatically and posttraumatically. In experiment 2, a 5-cm-long strip of skin was subcutaneously injected with 0.2 ml of 1% lidocaine near the incision site pretraumatically and posttraumatically. Flare, spontaneous pain, and primary and secondary hyperalgesia to punctate mechanical stimuli were assessed after the incision had been made. RESULTS: Pretraumatic lidocaine injection prevented the occurrence of spontaneous pain and development of flare formation that was found surrounding the incision site immediately (1 min) after the incision had been made. The lidocaine suppressed primary hyperalgesia more effectively than did posttraumatic block, but only for the first 4 h after the incision. The preincision block prevented development of secondary hyperalgesia, whereas posttraumatic block did not significantly affect the fully developed secondary hyperalgesia. The area of flare formation and the area of secondary hyperalgesia did not extend over the strip of the skin that had been pretraumatically anesthetized, whereas the posttraumatic block did not significantly reduce the area of fully developed secondary hyperalgesia. CONCLUSIONS: Pretraumatic injection of lidocaine reduces primary hyperalgesia more effectively than does posttraumatic injection, but only for a short period after incision. The spread of secondary hyperalgesia is mediated peripheral nerve fibers, but when secondary hyperalgesia has fully developed, it becomes less dependent on or even independent of peripheral neural activity originating from the injured site.     

Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks⁺ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks⁺ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks⁺ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks⁺ E. coli was more abundant in Stages 0–I tumor tissue than in normal mucosal tissue or in Stages II–IV tumor tissue. High abundance of pks⁺ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3–11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8–5.1, p < 0.001) in multivariable logistic analyses. Pks⁺ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7–25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3–7.3, p = 0.01) compared to the pks⁺ E. coli-high group. Pks⁺ E. coli was abundant in Stages 0–I CRC and associated with CRC prognosis. These results suggest that pks⁺ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.     

Asymptomatic isolated microhaematuria: natural history of 136 children

In a mass screening programme, 251 children with isolated microhaematuria were detected. Of these 251 children, 115 were excluded from the study because of microhaematuria, secondary to a specific cause. The remaining 136 children were diagnosed as having asymptomatic isolated microhaematuria (ASH). Of these 136 children, 23 had evidence of urinary abnormalities in their family members. Red blood cell casts were evident in 31 children at their initial visit or during the follow-up period. Ten children had one or more episodes of macrohaematuria during the study. Renal biopsy was performed in 19 children because of indications of glomerular discase, and 13 of these 19 children had mild to moderate glomerulonephritis. None of these 136 children developed hypertension or renal impairment after a mean period of 7.4 years (range 6–13 years). Thirty-five children had normal urinary findings within 6 years of their initial visit, and 100 have had persistent microhaematuria, without proteinuria throughout the follow-up period. The other child had microhaematuria with proteinuria greater than 1 g/m² per day at the end of the study. This study suggests that the prognosis of ASH is good and that renal biopsy is not indicated for children with ASH.     

Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation

Deoxyribonuclease (DNase) II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. DNase II-deficient mouse embryos accumulate undigested DNA in macrophages, and die in feto because of the activation of the interferon beta (IFNbeta) gene. Here, we found that the F4/80-positive macrophages in DNase II(-/-) fetal liver specifically produce a set of cytokines such as IFNbeta, TNFalpha, and CXCL10. Whereas, IFN-inducible genes (2'5'-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in macrophages but also in other F4/80-negative cells. When DNase II(-/-) macrophages or embryonal fibroblasts engulfed apoptotic cells, they expressed the IFNbeta and CXCL10 genes. The ablation of Toll-like receptor (TLR) 3 and 9, or their adaptor molecules (MyD88 and TRIF), had no effect on the lethality of the DNase II(-/-) mice. These results indicate that there is a TLR-independent sensing mechanism to activate the innate immunity for the endogenous DNA escaping lysosomal degradation.     

Interstitial magnetic resonance lymphography: comparative animal study of gadofluorine 8 and gadolinium diethylenetriamine-pentaacetic acid

PURPOSE: We evaluated the usefulness of gadofluorine 8 (G8) and gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA) for interstitial magnetic resonance lymphography (MRL). METHOD: Phantom imaging studies were conducted with G8 and Gd-DTPA corresponding to 0.1-0.005 micromol Gd/mL, and signal intensity was measured. Popliteal lymph node (PLN) accumulation was investigated in rabbits. Imaging was performed before and after subcutaneous administration of G8 (50 micromol Gd/mL) and Gd-DTPA (50 micromol Gd/mL). Contrast enhancement ratio measurements of PLN were determined both prior to and following the administration. RESULTS: Signal intensity of phantom for G8 are higher than those for Gd-DTPA from 0.1 to 0.002 micromol Gd/mL (P < 0.0001). Imaging after 5 minutes can clearly detect PLN accumulation on two contrast agents. Nevertheless, PLN accumulation of Gd-DTPA disappeared after about 30 minutes. A statistically significant difference between G8 and Gd-DTPA can be seen from 5 to 90 minutes in CER (P < 0.0001). PLN became clearly visible at 5 minutes after the injection of G8 and Gd-DTPA. Nevertheless, PLN accumulation of Gd-DTPA disappeared at 30 minutes. Otherwise, PLN accumulation of G8 continued up to 90 minutes. CONCLUSION: These studies indicated that G8 was more suitable than Gd-DTPA as a contrast agent for interstitial MRL up to 90 minutes.     

Phantom and animal studies of a new hepatobiliary agent for MR imaging: comparison of Gd-DTPA-DeA with Gd-EOB-DTPA

PURPOSE: To investigate the characteristics of Gd-DTPA-DeA as a hepatobiliary contrast agent for MR imaging in comparison with those of Gd-EOB-DTPA. MATERIALS AND METHODS: We undertook phantom experiments to assess T1 relaxivity for Gd-DTPA-DeA, Gd-EOB-DTPA, and Gd-DTPA in human plasma. For Gd-DTPA-DeA and Gd-EOB-DTPA, we evaluated the contrast effect in rats using an SPGR sequence. The contrast ratios of liver and abdominal aorta were measured up to 21 minutes after intravenous administration of the agents. Visualization of the bile duct and renal pelvis was also assessed. RESULTS: In human plasma, T1 relaxivity was similar for Gd-DTPA-DeA and Gd-EOB-DTPA, and higher than those for Gd-DTPA. Whereas the contrast ratio of liver peaked about five minutes after the injection of Gd-EOB-DTPA and was followed by a subsequent decline, a continuous rise was shown for Gd-DTPA-DeA, resulting in a larger maximal contrast effect. Contrast ratios of the abdominal aorta were larger for Gd-DTPA-DeA. Biliary excretion was observed for both agents but occurred earlier with Gd-EOB-DTPA. While renal excretion was shown for all rats three minutes after the injection of Gd-EOB-DTPA, it was not observed for Gd-DTPA-DeA. CONCLUSION: Gd-DTPA-DeA may be used as a hepatobiliary contrast agent and shows different pharmacokinetics from Gd-EOB-DTPA.     

Occurrence of ANTI-AHLG in renal transplant patients on AHLG (anti-human lymphocyte globulin)

Two patients with kidney transplants were prescribed anti-human lymphocyte γ-globulin (AHLG) as an adjunct immunosuppressive treatment. AHLG was prepared from cultured human lymphocytes as antigen and successive anti-AHLG levels were measured using passive hemagglutination tests during and after the AHLG treatment. Anti-AHLG levels began to increase after 10–14 days of daily AHLG administration. There-after, the levels tends to decrease transiently by the further administration of AHLG. The titer rose again after the discontinuation of AHLG administration reaching a plateau which continued for a considerable length of time. Pretreatment levels were reverted after more than three months. The anti-sheep RBC Ab and anti-horse RBC Ab levels followed the same pattern as that seen with anti-AHLG Ab. The anti-AHLG Ab proved to be specific anti-horse γ-globulin Ab. Alterations in the anti-AHLG levels can thus be used to monitor the optimal dosage and period of administration as well as to predict the anaphylactic reaction due to AHLG treatment. Keeping the anti-AHLG level low is mandatory to maintain good immuno-suppressive conditions yet avoid anaphylactic reactions.