Plasma cyclic nucleotide levels in acute leukemia patients

To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.     

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.     

神经外科中高渗盐注射液应用研究进展

控制脑水肿和颅内压(ICP)升高是神经外科围手术期治疗的重要组成部分.颅脑创伤、动脉梗塞、静脉高压/梗塞、大脑内出血、蛛网膜下腔出血、肿瘤和术后脑组织水肿的治疗过程中ICP的控制都是决定患者预后的关键因素.虽然利用渗透压脱水药物是控制ICP的最基础的工具,但却缺乏前瞻性研究以指导其运用,高渗盐被认为是甘露醇的替代物,早期的数据表明每种药的用药指征最终取决于ICP的病因.在这篇综述中,我们总结了有关高渗盐(HS)治疗颅内高压的相关数据,以及这些数据和我们有关HS的经验是如何指导目前的ICP治疗的.     

Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial

Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS^®, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. Research Design and Methods: This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dl (≤5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A_1c (HbA_1c). Results: Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA_1c decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (−1.4%, p < 0.001; algorithm 1 −1.3% vs. algorithm 2 −1.5%; p = 0.03) and glargine plus >1 OAD (−1.7%, p < 0.001; algorithm 1 −1.5% vs. algorithm 2 −1.8%; p = 0.001). Conclusions: This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA_1c with a low risk of hypoglycaemia. The greater reduction in HbA_1c was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.     

Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats

BACKGROUND & AIMS: Dietary nucleotides are reported to influence the growth and functioning of the liver and small intestine. The aim of this study was to examine the mechanism by which nucleotides exert their effects in these tissues by assessing protein synthesis activity and related parameters in the presence or absence of dietary nucleotides. METHODS: Rats were fed a purified diet with or without nucleotides for 10 days. Fractional protein synthesis rate, RNA and DNA concentrations, polysome size distribution, and number of ribosomes were assessed. RESULTS: Fractional protein synthesis rates of the liver and small intestine were lower in the nucleotide-deprived group than in the control group. In the liver, RNA concentration was also lower in the nucleotide-deprived group, but values in the small intestine were similar in the two groups. In the liver, deprivation of nucleotides resulted in a reduction in the number of ribosomes and in polysome breakdown. Protein and DNA concentrations did not vary in the liver; however, the concentration of DNA was lower in the small intestine of the nucleotide-deprived group than in the control group. CONCLUSIONS: Dietary nucleotides can modulate protein synthesis in the liver and small intestine as a result of tissue-specific nucleic acid changes. (Gastroenterology 1996 Jun;110(6):1760-9)     

Managing epilepsy well: self-management needs assessment

Epilepsy self-management interventions have been investigated with respect to health care needs, medical adherence, depression, anxiety, employment, and sleep problems. Studies have been limited in terms of representative samples and inconsistent or restricted findings. The direct needs assessment of patients with epilepsy as a basis for program design has not been well used as an approach to improving program participation and outcomes. This study investigated the perceived medical and psychosocial problems of adults with epilepsy, as well as their preferences for self-management program design and delivery format. Results indicated a more psychosocially challenged subgroup of individuals with significant depressive and cognitive complaints. A self-management program that involves face-to-face individual or group meetings led by an epilepsy professional and trained peer leader for 60 minutes weekly was preferred. Six to eight sessions focused on diverse education sessions (e.g., managing disability and medical care, socializing on a budget, and leading a healthy lifestyle) and emotional coping strategies delivered on weeknights or Saturday afternoons were most highly endorsed. Emotional self-management and cognitive compensatory strategies require special emphasis given the challenges of a large subgroup.