Low Phase Angle Is Correlated With Worse General Condition in Patients with Advanced Cancer

Objectives: Phase angle (PA) is a poor prognostic factor in patients with advanced cancer. This study aimed to identify possible correlations between PA and symptoms, quality of life, fluid retention, and laboratory data in cancer patients in palliative care settings.

Methods: Individuals who visited the outpatient clinic or were admitted to the palliative care unit were eligible. Patients with a performance status of 4 and/or those unable to complete questionnaires were excluded. PA was evaluated using a bioanalyzer device. The correlation coefficient between PA and the variables of interest was analyzed.

Results: A total of 102 patients were analyzed. PA was weakly correlated with age (ρ = ?0.22), performance status (ρ = ?0.30), functional well-being (ρ?=?0.20), anorexia/cachexia subscale (ρ?=?0.22), and Functional Assessment of Anorexia/Cachexia Therapy trial outcome index (ρ?=?0.26). PA was also correlated with fluid retention (ρ = ?0.34) and albumin (ρ?=?0.32), C-reactive protein (ρ = ?0.31), and hemoglobin (ρ?=?0.41) levels. Sub-analysis stratified according to sex revealed that males demonstrated the same results; however, female sex demonstrated a correlation between PA and social well-being (ρ = ?0.43).

Conclusions: PA was correlated with physical condition, but not with psychological well-being.     

Comparison of Indicators for Achievement of Pain Control With a Personalized Pain Goal in a Comprehensive Cancer Center

Context

The achievement of a personalized pain goal (PPG) is advocated as an individualized pain relief indicator.

Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion

IA-2 is a major autoantigen in type 1 diabetes. Autoantibodies to IA-2 appear years before the development of clinical disease and are being widely used as predictive markers to identify individuals at risk for developing type 1 diabetes. IA-2 is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is an integral component of secretory granules in neuroendocrine cells. To study its function, we generated IA-2-deficient mice. Northern and Western blot analysis showed that neither IA-2 mRNA nor protein was expressed. Physical examination of the IA-2(- /-) animals and histological examination of tissues failed to reveal any abnormalities. Nonfasting blood glucose levels, measured over 6 months, were slightly elevated in male IA-2(-/-) as compared to IA-2(+ /+) littermates, but remained within the nondiabetic range. Glucose tolerance tests, however, revealed statistically significant elevation of glucose in both male and female IA-2(-/-) mice and depressed insulin release. In vitro glucose stimulation of isolated islets showed that male and female mice carrying the disrupted gene released 48% (P < 0.001) and 42% (P < 0.01) less insulin, respectively, than mice carrying the wild-type gene. We concluded that IA-2 is involved in glucose-stimulated insulin secretion.     

Dense core vesicle proteins IA-2 and IA-2beta: metabolic alterations in double knockout mice

IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets. In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2beta(-/-)) to study the effect of the combined deletion of these two proteins on insulin secretion and blood glucose levels. The double knockout mice appeared healthy at birth and showed normal growth and development. Histological examination and immunostaining for insulin, glucagon, somatostatin, and pancreatic polypeptide revealed no difference between the double knockout and wild-type mice. Nonfasting blood glucose and insulin levels also were within the normal range. However, compared with the wild-type mice, the double knockout mice showed glucose intolerance and an absent first-phase insulin release curve. No evidence of insulin resistance was observed nor were there alterations in fasting blood glucose, insulin, or leptin levels in the double knockout mice maintained on a high-fat diet compared with the wild-type mice maintained on the same diet. In addition, to determine whether the combined deletion of IA-2 and IA-2beta played any role in the development of diabetes in NOD mice, we generated double knockout mice on the NOD/LtJ background. The incidence of diabetes in these mice was not significantly different than that in the wild-type mice. Taken together, our experiments show that the dense core vesicle proteins IA-2 and IA-2beta, alone or in combination, are involved in insulin secretion, but neither alone nor in combination are they required for the development of diabetes in NOD mice.     

Targeted disruption of the IA-2beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice

Insulinoma-associated protein (IA)-2beta, also known as phogrin, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is located in dense-core secretory vesicles. In patients with type 1 diabetes, autoantibodies to IA-2beta appear years before the development of clinical disease. The genomic structure and function of IA-2beta, however, is not known. In the present study, we determined the genomic structure of IA-2beta and found that both human and mouse IA-2beta consist of 23 exons and span approximately 1,000 and 800 kb, respectively. With this information, we prepared a targeting construct and inactivated the mouse IA-2beta gene as demonstrated by lack of IA-2beta mRNA and protein expression. The IA-2beta(-/-) mice, in contrast to wild-type controls, showed mild glucose intolerance and impaired glucose-stimulated insulin secretion. Knockout of the IA-2beta gene in NOD mice, the most widely studied animal model for human type 1 diabetes, failed to prevent the development of cyclophosphamide-induced diabetes. We conclude that IA-2beta is involved in insulin secretion, but despite its importance as a major autoantigen in human type 1 diabetes, it is not required for the development of diabetes in NOD mice.     

A Quantitative Evaluation of Hepatic Uptake on I-131 Whole-Body Scintigraphy for Postablative Therapy of Thyroid Carcinoma

This study aimed to determine clinical association between quantitative hepatic uptake on postablative whole-body scan (WBS) with differentiated thyroid cancer (DTC) prognosis.We analyzed 541 scans of 216 DTC patients who were divided into 3 groups based on radioactive iodine (I-131) WBS uptake and clinical follow-up: group 1 (completion of ablation), group 2 (abnormal uptake in the cervical region), and group 3 (abnormal uptake with distant metastases). For each group, we calculated the ratio of I-131 WBS hepatic uptake (H) to cranial uptake as background (B); this ratio was defined as H/B. Furthermore, we made a distinction between group 1, as having completed radioactive iodine therapy (RIT) (CR), and group 2 and 3, as requiring subsequent RIT (RR).The average H/B scores were 1.34 (median, 1.36; range 1.00–2.1) for group1; 1.89 (median, 1.75; range 1.41–4.20) for group 2; and 2.09 (median, 1.90; range 1.50–4.32) for group 3. Bonferroni multiple comparisons revealed significant differences in H/B among these groups. The H/B of group 1 was significantly smaller than that of other 2 groups (P < 0.0001). The precise cutoff value of H/B for therapeutic effect was ≤1.5. Moreover, 159 of 160 scans in the CR and 375 of 381 patients in the RR were correctly diagnosed using this cutoff value in the final outcome of RIT, yielding a sensitivity, specificity, positive predictive value, and negative predictive value of 99.4%, 98.4%, 99.7%, and 96.3%, respectively.Increased hepatic uptake of I-131 on WBS may predict disease-related progression.     

Absent skeletal uptake of <Superscript>99m</Superscript>Tc-hydroxymethylene diphosphonate in the presence of AL-type amyloidosis associated with multiple myeloma

A 66-year-old woman with congestive heart failure suspected to have multiple myeloma underwent bone scintigraphy. The bone scintigraphy using technetium-99m hydroxymethylene-diphosphonate showed the following interesting findings: absent skeletal uptake; increased gastrointestinal, myocardial, and soft tissue uptake; migration of radionuclide to bilateral pleural effusions. Histopathological examination revealed that the patient suffered from AL-type amyloidosis associated with multiple myeloma. Extraosseous uptake is often observed on bone scintigraphy in amyloidosis patients, but in many cases skeletal uptake is preserved. The simultaneous presentation of these findings is rare.     

Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility

Female infertility is a worldwide problem affecting 10-15% of the population. The cause of the infertility in many cases is not known. In the present report, we demonstrate that alterations in two transmembrane structural proteins, IA-2 and IA-2beta, located in dense core secretory vesicles (DCV) of many endocrine and neuroendocrine cells, can result in female infertility. IA-2 and IA-2beta are best known as major autoantigens in type 1 diabetes, but their normal function has remained an enigma. Recently we showed in mice that deletion of IA-2 and/or IA-2beta results in impaired insulin secretion and glucose intolerance. We now report that double knockout (DKO), but not single knockout, female mice are essentially infertile. Vaginal smears showed a totally abnormal estrous cycle, and examination of the ovaries revealed normal-appearing oocytes but the absence of corpora lutea. The LH surge that is required for ovulation occurred in wild-type mice but not in DKO mice. Additional studies showed that the LH level in the pituitary of DKO female mice was decreased compared with wild-type mice. Treatment of DKO females with gonadotropins restored corpora lutea formation. In contrast to DKO female mice, DKO male mice were fertile and LH levels in the serum and pituitary were within the normal range. From these studies we conclude that the DCV proteins, IA-2 and IA-2beta, play an important role in LH secretion and that alterations in structural proteins of DCV can result in female infertility.     

Hepatic clearance measured with 99mTc-GSA single-photon emission computed tomography to estimate liver fibrosis

AIM: To evaluate the clinical utility of hepatic clearance(HC) measured with technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl human serum albumin(99mTc-GSA) single-photon emission computed tomography(SPECT) to estimate the degree of liver fibrosis.METHODS:Seventy-eight consecutive patients who underwent initial hepatectomy due to hepatocellular carcinoma were enrolled in this study.Indocyanine green clearance(ICG R15),quantitative indices estimated by 99mTc-GSA[the receptor index(LHL15 and HH15)and HC via SPECT analysis],and conventional liver function tests were performed before hepatectomy.Correlations among the quantitative indices for liver functional reserve,conventional liver function tests,andthe degree of liver fibrosis were evaluated.RESULTS:The degree of liver fibrosis was correlated with ICG R15,HH15,LHL15,and HC.HC showed the best correlation with conventional liver function tests.According to multivariate analysis,HC and LHL15 were significant independent predictors of severe fibrosis.HC was the most valuable index for predicting severe fibrosis.CONCLUSION:HC measured with 99mTc-GSA SPECT is a reliable index for assessing liver fibrosis before hepatectomy.