Liposome‐Encapsulated Hemoglobin Ameliorates Ischemic Stroke in Nonhuman Primates: Longitudinal Observation

Liposome‐encapsulated hemoglobin (LEH) is protective early after brain ischemia in rats and nonhuman primates, but it remains unclear whether the protection persists and confers any benefits beyond the acute phase of brain ischemia and reperfusion. Ten monkeys underwent middle cerebral artery occlusion, received LEH (2 mL/kg, n = 5) or saline (2 mL/kg, n = 5) 5 min later, and reperfusion 3 h later. Positron emission tomography studies were repeated for the cerebral metabolic rate of O₂ (CMRO₂) as well as glucose (CMRglc) up to 8 days after reperfusion, when the animals were euthanized for morphological studies. There was no difference in O₂ metabolism until 3 h after reperfusion, when CMRO₂ was significantly better preserved in the cortex, but not in basal ganglia, on Day 0 in LEH‐treated monkeys. The extent of cortical infarction (saline 68 ± 10% vs. LEH 38 ± 9%, P < 0.05) and CMRO₂ (mild suppression: saline 34 ± 10% vs. LEH 14 ± 4%, P < 0.05) remained significantly better preserved 8 days later, when CMRglc showed a similar pattern of cortical protection (mild suppression: saline 49 ± 15% vs. LEH 37 ± 4%, P < 0.05) in LEH‐treated monkeys, together with regained body weight. Somatic weight control, morphological integrity, CMRO₂, and CMRglc were better preserved immediately, as well as 8 days after occlusion and reperfusion of the middle cerebral artery in monkeys receiving LEH early after onset of ischemia.     

Early evaluation of transcatheter arterial chemoembolization-refractory hepatocellular carcinoma

Background

There is no standard therapy for patients with transcatheter arterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC). This study examined whether evaluating the tumor effect (TE) at 1?week after TACE was useful for predicting refractoriness to TACE.

Methods

We performed a historical cohort study involving 54 patients and 119 tumors. TE was evaluated at 1?week and 3?months after TACE, and an overall evaluation was also performed at 3?months based on the response evaluation criteria in cancer of the liver.

Results

Among 45 tumors evaluated as TE2 at 1?week, 43 tumors (95.6%) were classified as TE1 or TE2 at 3?months. Of the 24 patients whose tumors were categorized as TE2 at 1?week, none achieved a complete or partial response.

Conclusions

Evaluating the TE at 1?week after TACE is useful for the early diagnosis of TACE-refractory HCC and allows alternative treatment options, such as sorafenib, to be employed before the disease progresses.     

Falsely elevated thyroid hormone levels caused by anti-ruthenium interference in the Elecsys assay resembling the syndrome of inappropriate secretion of thyrotropin

The syndrome of inappropriate secretion of thyrotropin (SITSH) is defined as the inappropriate non-suppression of serum TSH in the presence of elevated free thyroid hormone; TSH-secreting pituitary adenomas and the syndrome of resistance to thyroid hormone are the main etiologies of SITSH. In addition, erroneous thyroid function testing may result in the diagnosis of this syndrome. A 63-year-old woman was referred because of suspected SITSH. Laboratory tests showed a normal TSH (0.52 μIU/L; normal range: 0.5-5.0) measured by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6) and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive Elecsys. To exclude possible assay interference, aliquots of the original samples were retested using a different method (ADVIA Centaur), which showed normal FT4 and FT3 levels. Eight hormone levels, other than thyroid function tests measured by competitive or sandwich Elecsys, were higher or lower than levels determined by an alternative analysis. Subsequent examinations, including gel filtration chromatography, suggested interference by substances against ruthenium, which reduced the excitation of ruthenium, and resulted in erroneous results. The frequency of similar cases, where the FT4 was higher than 3.2 ng/dL, in spite of a non-suppressed TSH, was examined; none of 10 such subjects appeared to have method-specific interference. Here, a patient with anti-ruthenium interference, whose initial thyroid function tests were consistent with SITSH, is presented. This type of interference should be considered when thyroid function is measured using the Elecsys technique, although the frequency of such findings is likely very low.     

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non‐elderly using a visual analogue scale: The importance of appetite and depressive mood

Aim: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. Methods: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non‐elderly) and compared the difference between elderly and non‐elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3‐year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self‐evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)‐15. Results: There was no difference in VAS scores between elderly and non‐elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non‐elderly. VAS scores for mood correlated with GDS‐15 in HD patients. Conclusions: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non‐elderly. Geriatr Gerontol Int 2012; 12: 65–71.     

Localized Neurofibromas in the Bilateral Orbits

Localized neurofibromas are rare in the orbit and, unlike the more common plexiform neurofibromas, are not typically associated with von Recklinghausen neurofibromatosis. We present a rare case of localized neurofibromas in the bilateral orbits.     

Feedback-controlled bolus plus infusion (FC-B/I) method for quantitative drug assessment in living brain with PET

We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for monitoring the interaction between positron emission tomography (PET) ligands and their specific target molecules with PET. The usefulness of the FC-B/I method was evaluated by the direct interaction between [¹¹C]raclopride, a dopamine D₂ receptor (D₂R) ligand, and cold raclopride (10 and 100 μg/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [¹¹C]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [¹¹C]raclopride binding to D₂R was observed in a dose-dependent manner. Good correlations of distribution volume ratio of the striatum to cerebellum between the conventional bolus plus infusion (B/I) method and the FC-B/I method as well as between the conventional bolus injection method and the FC-B/I method were observed. These results indicated that the system could be a useful tool for the evaluation of interaction between drug candidates and their target molecules like enzymes, receptors, and transporters by using of their specific PET ligands.     

Surgical Apgar Score Predicted Postoperative Morbidity After Esophagectomy for Esophageal Cancer

Background

Recently, a simple and easy complication prediction system, the Surgical Apgar Sore (SAS) calculated by three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. This study aimed to determine if the SAS could accurately predict perioperative morbidity in patients undergoing esophagectomy for esophageal cancer.

Methods

We investigated 399 patients who underwent esophagectomy at the Kumamoto University Hospital between April 2007 and March 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Patients had postoperative morbidities classified as Clavien–Dindo grade III or more. Univariate and multivariate analyses were performed to elucidate factors that affected the development of complications.

Results

The mean age of the study population was 65.7 years, 357 patients (89.5 %) were male. The frequency of any morbidity was 32.3 %. Univariate analyses showed that the SAS as well as preoperative chemotherapy, volume of bleeding, and reconstruction of organs were associated with morbidities. Multivariate analysis showed that a SAS < 5 was found to be an independent risk factor for morbidities.

Conclusion

The SAS is considered to be useful for predicting the development of postoperative morbidities after esophagectomy for esophageal cancer.