Glibenclamide induced prolonged hypoglycaemia

Prolonged hypoglycaemia (serum glucose levels of 50 mg/dl and less, for more than 12 h in spite of treatment with periodic injections of hypertonic glucose) secondary to treatment with glibenclamide was found in 13 hospitalized patients. The mean daily dose of glibenclamide was 6.7 mg. In nine patients, the hypoglycaemia developed within 7 days of treatment. In two patients the tendency to hypoglycaemia lasted for more than 60 h in spite of continuous infusion of 5% or 10% glucose. Old age seems to be a crucial predisposing factor as none of the patients was under the age of 68 years. Contributing factors were renal failure and congestive heart disease. We feel that glibenclamide should be used with care in the elderly and in patients with renal or cardiac failure.     

10 K: a large‐scale prospective longitudinal study in Israel

European Journal of Epidemiology - The 10 K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development...     

Prediction of acute-coronary-syndrome using newly-defined R2-CHA2DS2-VASc score among patients with chest pain

BackgroundChest-pain patients with no evidence of acute coronary syndrome might still be at risk for adverse outcomes. Adding renal function to the classic scoring of CHADS and CHA₂DS₂ VASC may improve risk stratification of chest-pain patients discharged from internal medicine wards after acute coronary syndrome (ACS) rule-out.MethodsWe accessed medical records of patients admitted to internal medicine wards during 2010–2016 and discharged following ACS rule-out. A R₂CHA₂DS₂-VASc score model that included higher scores as kidney function deteriorated was calculated and compared to CHADS and CHA₂DS₂ VASC scores. The primary endpoint was the composite of 30-day ACS and mortality. One-year ACS and 1-year mortality were the secondary endpoints. The study included 12,449 patients, stratified into three risk groups according to their R₂CHA₂DS₂-VASc score.ResultsParticipants were stratified into 3 groups according to R₂CHA₂DS₂-VASc score. R₂CHA₂DS₂-VASc score predicted better the composite outcome of ACS and 30-day and 1-year mortality after discharge (OR: 4, 95%, CI 2.3–7, p < 0.01 and OR: 13.3, 95% CI 7.8–22.7, p < 0.01, respectively). Receiver operating characteristic curve analysis showed better risk stratification of the R₂CHA₂DS₂-VASc compared with both CHADS and CHA₂DS₂ VASC score.ConclusionsThe R₂CHA₂DS₂-VASc score is a better predictor of short- and long-term cardiovascular morbidity and mortality after hospital discharge.     

Specific Antibodies Compared to Cross-Reacting Antibodies in ABO Incompatibility

Abstract. The purpose of the present work was to determine the significance of specific antibodies, as compared to cross-reacting antibodies in causing the hemolytic disease of the newborn in cases of ABO incompatibility. Fifteen cases of severe icterus, including twelve who had received exchange transfusion and two cases of ante partum fetal death, were investigated. The amount of anti A, anti B, and cross-reacting antibodies was assayed in maternal blood within 48 h after delivery. Specific antibodies were found more consistently and in higher titres than cross-reacting antibodies. It therefore seems reasonable to assume that these are the antibodies responsible for the development of the disease in the newborn in our cases.     

Experimental Model to Study the Role of Retinoblastoma Gene Product (pRb) for Determination of Adipocyte Differentiation

Bulletin of Experimental Biology and Medicine - Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines...     

Regulation of counterregulatory hormone secretion in man during exercise and hypoglycemia

We examined the role of the plasma glucose concentration per se in the secretion of counterregulatory hormones during exercise. Ten men (average age, 24 yr; maximal aerobic capacity, 31.8 mL/kg.min) were studied during two 50-min bicycle exercise periods at either normal glucose [87 +/- 1 (+/- SE) mg/dL (4.8 +/- 0.1 mmol/L)] or low glucose [59 +/- 1 mg/dL (3.3 +/- 0.1 mmol/L)]. The plasma glucose targets were achieved by exogenous insulin and variable glucose infusions. These results were compared to studies in which saline was infused. Exercise at normal glucose was associated with significant increments in plasma epinephrine (maximum 3- to 5-fold above baseline) and norepinephrine (2-fold), comparable to those that occurred during saline administration. Plasma GH increased only at the most intense exercise level, while plasma cortisol and glucagon did not increase significantly. In low glucose-exercise studies, the increase in plasma epinephrine during exercise was significantly greater than that at normal glucose (P less than 0.01), although proportional to basal preexercise levels (r = 0.73; P less than 0.001). Plasma glucagon increased almost 100%, and plasma cortisol and GH increased by 150% and 400%, respectively. Compared to the effect of the same degree of hypoglycemia in the absence of exercise, only plasma epinephrine (P = 0.002) and norepinephrine (P less than 0.001) displayed effects independent of hypoglycemia during exercise. When low glucose was reversed to normal at the midpoint of exercise, plasma epinephrine and glucagon returned to the levels obtained for the same duration of exercise at normal glucose, while norepinephrine, GH, and cortisol were only partially responsive to the rise in plasma glucose. These data suggest that 1) moderate exercise is a stimulus for a sympathoadrenal and GH response, but not a peripheral glucagon response; 2) during exercise and hypoglycemia, plasma epinephrine and norepinephrine are enhanced, while the glucagon response is entirely glucose dependent; and 3) the epinephrine response to hypoglycemia can be dissociated from that to exercise, suggesting differing control mechanisms. We conclude that the activation of counterregulatory hormones during exercise is regulated by glucose-independent mechanisms, although these responses may be augmented by concurrent hypoglycemia.     

Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC. We observed expression of CB1 (24%) and CB2 (55%) in NSCLC patients. Furthermore, we have shown that the treatment of NSCLC cell lines (A549 and SW-1573) with CB1/CB2- and CB2-specific agonists Win55,212-2 and JWH-015, respectively, significantly attenuated random as well as growth factor-directed in vitro chemotaxis and chemoinvasion in these cells. We also observed significant reduction in focal adhesion complex, which plays an important role in migration, upon treatment with both JWH-015 and Win55,212-2. In addition, pretreatment with CB1/CB2 selective antagonists, AM251 and AM630, prior to JWH-015 and Win55,212-2 treatments, attenuated the agonist-mediated inhibition of in vitro chemotaxis and chemoinvasion. In addition, both CB1 and CB2 agonists Win55,212-2 and JWH-133, respectively, significantly inhibited in vivo tumor growth and lung metastasis (～50%). These effects were receptor mediated, as pretreatment with CB1/CB2 antagonists abrogated CB1/CB2 agonist-mediated effects on tumor growth and metastasis. Reduced proliferation and vascularization, along with increased apoptosis, were observed in tumors obtained from animals treated with JWH-133 and Win55,212-2. Upon further elucidation into the molecular mechanism, we observed that both CB1 and CB2 agonists inhibited phosphorylation of AKT, a key signaling molecule controlling cell survival, migration, and apoptosis, and reduced matrix metalloproteinase 9 expression and activity. These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC.     

A case of indirect cauda equina syndrome from metastatic prostate cancer

We report the case of a patient with metastatic hormone refractory prostate cancer in whom “indirect” cauda equina syndrome developed concurrent with multilevel spinal cord compression (SCC). Three months after his first positive bone scan, a 65-year-old otherwise healthy man presented with severe back pain, bilateral lower extremity paresthesias, leg weakness and urinary retention. Magnetic resonance imaging (MRI) showed a dural-based mass causing SCC at the T9, T10 and T11 vertebrae, with a normal cauda equina. He received corticosteroids and palliative external beam radiotherapy, resulting in good pain control and gradual improvement in his neurological symptoms. He did well for 8 months, at which time his residual bilateral leg weakness abruptly worsened and he experienced numbness, paresthesias, urinary incontinence and constipation. Repeat MRI showed progression of epidural metastatic disease compressing the spinal cord or thecal sac at 7 thoracic vertebral levels. The cauda equina was also distorted and flattened without evidence of direct solid tumour impingement. We hypothesized that the etiology was increased intrathecal pressure due to disrupted cerebrospinal fluid flow resulting from multiple levels of upstream thecal sac compression. It is essential to image the entire spinal cord and cauda equina when patients with metastatic bone disease present with neurological symptoms to institute correct treatment and preserve function and mobility.