Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study.

PURPOSE: Achieving biochemical control (normalization of insulin-like growth factor-1 [IGF-1] and growth hormone [GH]) is a key goal in acromegaly management. However, IGF-1 and GH fluctuate over time. The true potential impact of time-varying biochemical control status on comorbidities is unclear and relies on multiple, longitudinal IGF-1 and GH measurements. This study assessed the association between time-varying biochemical control status and onset of selected comorbidities in patients with acromegaly. METHODS: Medical charts of adults with confirmed acromegaly and ≥ 6 months of follow-up at an Italian endocrinology center were reviewed. Patients were followed from the first diagnosis of acromegaly at the center until loss to follow-up, chart abstraction, or death. Biochemical control status was assessed annually and defined as IGF-1 ≤ the upper limit of normal, or GH ≤ 2.5 µg/L in the few cases where IGF-1 was unavailable. Time-varying Cox models were used to assess the association between biochemical control status and comorbidities. RESULTS: Among 150 patients, 47% were female, average age at diagnosis was 43.1, and mean length of follow-up was 10.4 years. Biochemical control was significantly associated with a lower hazard of diabetes (HR = 0.36, 95% CI 0.15; 0.83) and cardiovascular system disorders (HR = 0.54, 95% CI 0.31; 0.93), and a higher hazard of certain types of arthropathy (HR = 1.68, 95% CI 1.04; 2.71); associations for other comorbidities did not reach statistical significance. CONCLUSION: Results further support the importance of achieving biochemical control, as this may reduce the risk of high-burden conditions, including diabetes and cardiovascular system disorders. The association for arthropathy suggests irreversibility of this impairment. Due to limitations, caution is required when interpreting these results.

[The clinical significance of plasma PTX3 in patients with secondary hemophagocytic lymphohistiocytosis].

Objective: To investigate the significance of plasma pentraxin 3 (PTX3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). Methods: Plasma PTX3 levels were tested by ELISA in 48 newly diagnosed sHLH patients, 18 healthy volunteers and 9 lymphoma controls in the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2019. Clinical parameters were collected, and the correlations with PTX3 levels were analyzed. Results: PTX3 level in newly diagnosed group was significantly higher than that of healthy control group [16.29(1.17-66.00) vs. 0.76(0.01-7.86) µg/L, P<0.01]. Patients with lymphoma-associated HLH(LHLH) had higher plasma level of PTX3 than Fhose with infection-associated HLH (IHLH) [24.29(3.36-66.00) vs. 9.56(1.17-36.50)µg/L, P<0.05]. Plasma PTX3 levels in 48 sHLH patients were positively correlated with serum ferritin (P<0.05). Receiver operating characteristic (ROC) curve for plasma PTX3 levels of sHLH and healthy controls produced a cutoff value at 3.9 µg/L, with its 86.7% sensitivity and 94.4% specificity. And ROC analysis showed that PTX3 17.5 µg/L was the critical value for diagnosis of LHLH from non-LHLH group, that the sensitivity and specificity were 63.0% and 76.2% respectively. The 1-year overall survival (OS) rate in patients with PTX3≥17.5 µg/L was significantly lower in those with PTX3<17.5 µg/L (18.5% vs. 75.8%, P<0.01). Conclusion: These results indicate the potential of PTX3 as a biomarker for diagnosis and prognosis in patients with sHLH.

Characterization of Dicrocoelium dendriticum isolates from small ruminants in Shaanxi Province, north-western China, using internal transcribed spacers of nuclear ribosomal DNA.

The genetic variations in internal transcribed spacers (ITS) spanning ITS-1, 5.8S and ITS-2 rDNA of Dicrocoelium dendriticum, isolated from sheep and goats in four geographical regions in Shaanxi province, were examined. The lengths of ITS-1, 5.8S and ITS-2 rDNA sequences for D. dendriticum were 749 bp, 161 bp and 234 bp, respectively. Intra-specific sequence variations of D. dendriticum were 0-0.5% for ITS-1 and 0-1.3% for ITS-2 rDNA, while the inter-specific variations among species in genus Dicrocoelium in ITS-2 rDNA were 3.4-12.3%. Phylogenetic analysis based on sequences of ITS-2 rDNA showed that all D. dendriticum isolates in the present study were grouped with reference D. dendriticum isolates from sheep and goats, and D. dendriticum isolates from cattle and Japanese serow were clustered in a sister clade. However, the phylogenetic tree could not reveal geographically genetic relationships of D. dendriticum isolates in different origins and hosts. These findings provided basic information for further study of molecular epidemiology and control of D. dendriticum infection in Shaanxi province as well as in the world.

Molecular approaches to differentiate three species of Nematodirus in sheep and goats from China based on internal transcribed spacer rDNA sequences.

Internal transcribed spacer (ITS) rDNA sequences of three Nematodirus species from naturally infected goats or sheep in two endemic provinces of China were analysed to establish an effective molecular approach to differentiate Nematodirus species in small ruminants. The respective intra-specific genetic variations in ITS1 and ITS2 rDNA regions were 0.3-1.8% and 0-0.4% in N. spathiger, 0-6.5% and 0-5.4% in N. helvetianus, and 0-4.4% and 0-6.1% in N. oiratianus from China. The respective intra-specific variations of ITS1 and ITS2 were 1.8-4.4% and 1.6-6.1% between N. oiratianus isolates from China and Iran, 5.7-7.1% and 6.3-8.3% between N. helvetianus samples from China and America. For N. spathiger, compared with samples from China, sequence differences in ITS1 rDNA were 0.3-2.4% in isolates from America, 0.3-2.9% in New Zealand and 2.1-2.4% in Australia. Genetic variations in ITS2 rDNA of N. spathiger were 0-0.4% between samples from China and America, and 0-0.8% between samples from China and New Zealand. Using mutation sites, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and specific PCR techniques were developed to differentiate these three Nematodirus species. The specific PCR assay allowed the accurate identification of N. oiratianus from other common nematodes with a sensitivity of 0.69 pg and further examination of Nematodirus samples demonstrated the reliability of these two molecular methods.

The role of provider characteristics on the hepatitis A and B vaccination status of adults in the United States during 2007-2015.

Hepatitis A and B vaccine coverage is suboptimal in US adults, even among those at increased risk for infection, morbidity, or mortality. To understand where medical education and resources might enhance vaccine coverage, it is important to first identify providers and places most commonly associated with the administration of hepatitis vaccinations. We conducted a retrospective analysis of commercial and Medicare insurance claims data from 2007 to 2015 to describe provider types and places of vaccination against hepatitis A and B among adults in the US, and estimated the time to initial vaccination from first diagnosis of a condition for which the Advisory Committee on Immunization Practices (ACIP) recommends hepatitis A and/or B vaccination among at-risk adults. We identified 183,326 adults who received hepatitis A vaccine, 148,119 hepatitis B vaccine, and 64,953 a bivalent vaccine. Mean age was 42.1-45.8 years. Family practice and internal medicine physicians were the main vaccine providers: 38.9% and 20.2% for hepatitis A, 43.7% and 21.4% for hepatitis B, 35.3% and 15.9% for bivalent vaccinations, respectively. ≥90% of initial vaccinations occurred in an office practice. In at-risk patients, median time to first-dose received was 11.8, 20.9, and 20.9 months for hepatitis A, hepatitis B, and hepatitis A/B vaccines, respectively. Primary care and office practices were the most common providers and places of vaccination, respectively, for hepatitis A and B vaccine. For at-risk patients, further research is needed to design vaccination strategies to improve the median time from first ACIP-recommended condition diagnosis to initial vaccination against hepatitis A and B.

[Clinical analysis of secondary hemophagocytic lymphohistiocytosis complicated with capillary leak syndrome].

Objective: To investigate the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) . Methods: The clinical and laboratory data of 87 sHLH patients, who were treated in our hospital between January 2015 and December 2017, were retrospectively analyzed. Depending on whether they were complicated with CLS, 21 sHLH patients were classified as the CLS-sHLH group, while 66 were classified as the non-CLS-sHLH group. The differences of clinical manifestations, laboratory tests, treatment and prognosis between the two groups were compared. Results: There was no significant difference in the etiology of sHLH between the CLS-sHLH group and the non-CLS-sHLH group (P>0.05) . The neutrophil, fibrinogen and albumin levels in the CLS-sHLH group were lower than those in the non-CLS-sHLH group, while the triacylglycerol levels were higher than those in the non-CLS-sHLH group (P<0.05) . Varying degrees of edema, weight gain, hypotension, hypoproteinemia, oliguria and multiple serous effusions were observed in the CLS-sHLH group. Among them, there were 15 patients that CLS get improved, and the medial time of improvement was 7 (5-14) days. The other 6 patients did not get remission, while they died within 6-30 days. The median overall survival of the CLS-sHLH group was lower than that of the non-CLS-sHLH group (75 days vs not reached, P=0.031) . Conclusions: There may be no correlation between the cause of sHLH and the occurrence of CLS. Severity of neutropenia, fibrinogen and albumin levels, and triglyceride levels may be accompanied for sHLH patients complicated with CLS. Patients with sHLH who complicated with CLS have a poor prognosis. Active treatment of HLH and its primary disease, reasonable fluid replacement and oxygen supply are crucial, which can effectively control disease progression.

The abnormality of glucose transporter in the erythrocyte membrane of Chinese type 2 diabetic patients.

Type 2 diabetes mellitus is characterized by impaired glucose uptake. With a photometric method of recording the erythrocyte suspension absorption during the course of glucose transport across the membranes, we observed that the initial rate of glucose zero-trans entry was decreased significantly in 30 Chinese type 2 diabetic patients as compared to 25 healthy controls. The rate of glucose infinite-cis efflux exhibited no difference between the patients and controls. The measurement of temperature dependence of glucose transport showed that the activation energy for glucose entry was increased in diabetic patients. The inhibitory constant of glucose entry by cytochalasin B (CB) in patients was similar to that of the controls. However, we found that the inhibitory constant was increased significantly in the patient erythrocytes after phloretin treatment. After the erythrocytes were made into stripped white ghosts, the fluorescence quenching experiment was performed. Glucose, CB and phloretin can quench the fluorescence of tryptophan residues in the glucose transporter 1, GLUT1. The abnormality of fluorescence quenching in the erythrocyte membranes of patients was observed. The transfer tendency of tryptophan residues from the hydrophilic environment to the hydrophobic environment was decreased in patient ghosts as binding with glucose, and the opposite tendency appeared as CB and phloretin instead of glucose. We conclude that the decreased in glucose entry in the erythrocyte membranes of diabetic patients was due to the GLUT1 change in structure - mostly the outer domain of the glucose transporter.

A calorie-restriction diet supplemented with fish oil and high-protein powder is associated with reduced severity of metabolic syndrome in obese women.

BACKGROUND/OBJECTIVES: The prevalence of metabolic syndrome (MetS) and obesity has increased worldwide, as well as in Taiwan, particularly in women aged>40 years. The purpose of this study was to elucidate the effects of a calorie-restriction diet (CR) supplemented with protein and n-3 polyunsaturated fatty acids (PUFAs) on women with MetS. SUBJECTS/METHODS: A total of 143 eligible female participants were recruited and assigned to four dietary interventions such as 1500-kcal CR, calorie-restriction meal-replacement diet (CRMR), calorie-restriction diet with fish oil supplementation (CRF) and calorie-restriction meal-replacement diet with fish oil supplementation (CRMRF). The changes in anthropometric measures, metabolic profiles, inflammatory response and the Z-score of severity of MetS were evaluated. RESULTS: Among 143 female MetS patients enrolled, 136 patients completed the 12-week study. After the 12-week dietary interventions, we observed reductions in body weight (BW), body mass index (BMI) and waist circumference (WC) in all groups. BMI and triglyceride (TG) levels decreased significantly in the CRMR, CRF and CRMRF groups, but not in the CR group. The homeostasis model assessment of insulin resistance (HOMA-IR) had significantly improved in all four groups, and the levels of interleukin-6 (IL-6) and C-reactive protein (CRP) had significantly decreased in the CRF and CRMRF groups. Following the interventions, the changes in waist circumference (WC), mean arterial pressure (MAP), fasting blood glucose (FBG), TGs, HOMA-IR, CRP and IL-6 significantly correlated with the reductions in Z-score of MetS severity. CONCLUSIONS: Our study results indicate that a calorie-restriction dietary intervention combined with various macronutrients can reduce the severity of MetS in women and increase recovery from MetS by almost twofold in comparison with a CR alone.

Quantitative sensory testing and risk factors of diabetic sensory neuropathy.

The goal of this study was to identify risk factors for diabetic peripheral sensory neuropathy in type 2 diabetes mellitus in a Chinese population. Peripheral sensory neuropathy was detected by quantitative sensory testing (5.07/10 g monofilament, neurometer and 128-Hz Riedel Seiffert graduated tuning fork). Those who had two or more abnormal quantitative sensory testings were defined as having diabetic sensory neuropathy. Of the 558 non-insulin dependent diabetes mellitits subjects, 62 (11.1%) had peripheral neuropathy. In 59 (10.6%) detection was by monofilament testing, 45 (8.1%) by graduated tuning fork, and 189 (33.9%) by neurometer. In a multivariate logistic regression model, age and insulin therapy were significantly associated with peripheral neuropathy. Age, serum triglyceride, height, and fasting plasma glucose were independently associated with large fiber neuropathy. Our results confirm the previously identified multiple risk factors of diabetic neuropathy. Different quantitative sensory testings detect different nerve fiber defects. The weak correlation between these tests indicates the need to use more than one test in screening for diabetic neuropathy.

The physiological state as a modifier of radiation-induced cytotoxicity in heterogeneous murine tumor cells growing in vitro.

The oxic radiation response (cytotoxicity) of two heterogeneous murine tumor-cell lines cultured in vitro was studied as a function of the cell's physiological state at the time of X-irradiation. The proliferating (P) 66 and 67 cells displayed equal radiosensitivities; however, the quiescent (Q) cells were considerably more radiosensitive than the P cells, and the 66Q cells were even more radiosensitive than the 67Q cells. Also, the 66Q cells continued to proliferate slowly with about 85 per cent in the G1 phase and 10 per cent in the S phase, while the 67 Q cells displayed a more complete G1 arrest (92-95 per cent). A detailed analysis of the metabolic status vs cell-cycle age (i.e. G1 vs S phase) indicated that the cell-cycle age was the predominant factor influencing radiation-induced cytotoxicity in 67 cells. The data also showed that in the plateau phase Q-cell cultures, pH and cell contact were not influencing factors and that the increased radiosensitivity of the Q cells could not be explained on the basis of energy deprivation. Moreover, the 66Q, but not the 67Q cells displayed an increased sensitivity in addition to that caused by the predominant cell-cycle age shift. This extra increase in radiosensitivity is of unknown metabolic origin, but could be related to cellular membrane fragility in the stressed 66Q cells since this extra component of Q-cell radiosensitivity was reduced both by refeeding (metabolic activation) 4 h before X-irradiation and by delayed plating while incubating the cells in Q medium at 37 degrees C after X-irradiation.

Adrenal cancer with hypertension but low plasma renin and aldosterone.

Patients with malignant lesions of the adrenal gland may present with a syndrome of excess mineralocorticoids. Both primary hyperaldosteronism and excess mineralocorticoids other than aldosterone resulting from adrenal carcinoma have rarely been reported. In most patients with adrenal tumors secreting mineralocorticoids other than aldosterone, distant metastasis had already occurred at the time of diagnosis and the prognosis was poor. We present a rare case of adrenal cancer with hypertension in a patient with low plasma renin activity and a low plasma aldosterone concentration. The patient's blood pressure returned to normal after removal of the tumor. The patient is still alive and without recurrence 6 years after surgery. This case illustrates the value of thorough evaluation of hypertension and prompt surgical treatment for patients with adrenal cancer.

Effects of reducing sympathetic activities on acute myocardial ischemia in cats.

The importance of the sympathetic nervous system in the genesis of ventricular arrhythmias associated with acute myocardial ischemia (AMI) was assessed in urethane-chloralose anesthetized cats. AMI was created by a ligation of the left anterior descending coronary artery. All control cats developed ventricular tachyarrhythmia (VT), ventricular fibrillation (VF), bradycardia and hypotension, resulting in 50% mortality. In other groups the paramedian reticular nucleus (PRN) was intermittently stimulated to inhibit the sympathetic nervous system. Both sides of the stellate ganglia (SG) or adrenal glands (AG) were removed to exclude direct effects of cardiac sympathetic nerve or indirect effects of circulatory catecholamines from the adrenal medulla on the heart, respectively. AMI did not affect plasma norepinephrine (NE) and epinephrine (EPI) concentrations in all groups. However, NE concentration was higher in SG removed but lower in AG removed group. Removal of SG and stimulation of PRN significantly reduced arrhythmia score and the incidence of VT, VF and mortality. Removal of AG appeared to be less effective. These findings suggest that cardiac sympathetic innervation is more important than neural and adrenal catecholamine secretions in the plasma.

[Synthesis and cardiovascular activities of peptidyl dopamine derivatives].

Amino acids and small peptides with different steric configurations and lipophilicities were appended to dopamine. Eighteen compounds have been synthesized. The attachment of D-amino acids or N-methyl amino acids onto the dopamine molecule caused a marked decrease in cardiovascular activity by intravenous injection, while the introduction of lipophilic amino acids caused a marked increase in myocardial contractility and blood pressure in anesthetized dogs. The durations of action were also prolonged.

[Evaluation of positron emission tomography in diagnosing and staging of lung cancer].

OBJECTIVE: To evaluate positron emission tomography (PET) in diagnosing and staging of lung cancer. METHODS: One hundred and forty-seven patients (93 with lung cancer, 15 with lung metastatic tumors, 39 with benign lesions) were involved in the study. 163 whole body examinations (twice in 12 cases and 3 times in 2 cases) were performed after injection of 18F-fluro-deoxy-glucose (18FDG) with a Siemens ECAT EXACT HR + PET system. The results of PET were compared with pathological diagnoses (112 cases), clinical follow-up (35 cases), CT (68 malignant and 30 benign cases), and other imaging diagnoses. RESULTS: For the 147 cases with lung lesions, the sensitivity, specificity, and accuracy of FDG PET in differentiating the malignant from the benign were 97.2%, 89.7%, and 94.6% respectively. For the 93 lung cancer cases, more lesions were detected by PET in 58 (62.4%) cases, and changed staging in 36 (38.7%). In the 98 cases examinations, PET positive findings were consistent with CT in 39 (39.8%) cases; PET detected more lesions than CT in 29 (29.6%) cases; the lesions detected by CT were negative or with low uptake in the PET images in 30 (30.6%) cases, and they were finally proved as benign by follow-up. However, CT provided better detailed anatomical structures of the lesions than PET, and image fusion should give more information about the lesions. CONCLUSIONS: FDG PET had advantages in diagnosing and staging of lung cancer by providing metabolic information of the lesions. Comparison and fusion of PET with CT will give much help to clinical diagnosis.