Down''s syndrome is strongly associated with coeliac disease

BACKGROUND: Investigations recording recovery times of muscle relaxants have used initial or final baseline of a neuromuscular trace, or both, as a reference for data analysis. We evaluated the use of final baseline of EMG traces as a reliable reference to calculate recovery times. METHODS: We analyzed EMG traces from 82 children who had full spontaneous neuromuscular recovery following a single dose of mivacurium. Times from administration of mivacurium to 25, 50, 75, and 90% EMG recoveries were measured using both initial and final baselines as a reference. EMG traces with final baseline of 100 +/- 10% of the initial baseline were regarded as optimal. Recovery times from all other traces were compared to the times obtained from these optimal traces. Poor final baseline was defined as that of < 80% of initial baseline. Inter-group comparisons were made using Kruskal-Wallis test followed by Mann-Whitney U tests. RESULTS: EMG recovery times were similar for optimal traces whether the reference was the initial or the final baseline of the EMG trace. If the final baseline was used as the reference, then traces with poor final EMG baseline also showed similar neuromuscular recovery times. If the initial baseline was used as the reference for EMG traces with poor final baseline, then neuromuscular recovery times became 24-55% longer (P < 0.05). CONCLUSIONS: We conclude that the final baseline of an EMG trace can be used as a reference for calculations of neuromuscular recovery times following a bolus injection of mivacurium.     

Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis

Insulin resistance syndrome (IRS) has the potential to explain a large group of common metabolic and cardiovascular disorders [e.g., obesity, non-insulin-dependent diabetes mellitus (NIDDM), hypertension, hyperlipidaemia, hypercoagulability] which are all in themselves cardiovascular risk factors. This contribution firstly reviews the convincing evidence from glucose-clamp studies that all of these conditions are characterised by the presence of combined insulin resistance and hyperinsulinaemia, and secondly examines the relationships of the components of this syndrome to coronary artery disease and to the rational choice of antihypertensive therapy.     

Plasma leptin is not associated with insulin resistance and proinsulin in non-diabetic South Asian Indians

In an earlier study, we observed only a weak association between plasma insulin (non-specific assay) and leptin in South Asian Indians. This was in contrast to the observations in many other ethnic groups. With the availability of measurements of specific insulin (SI) and proinsulin (PI) in the same study group, we have reanalysed the data to look for possible correlation of leptin with proinsulin and with insulin resistance calculated from the fasting values of specific insulin and glucose using the HOMA model. Subjects with normoglycaemia (n = 117) and impaired glucose tolerance (n = 27, WHO criteria) were included in the analysis. Leptin values were higher in women. Multiple linear regression analysis showed that the variations in leptin concentrations in men were associated with BMI, WHR, and 2 h SI values (R2 = 56.2%) while fasting SI and proinsulin concentrations had no significant association. In women BMI and age showed a significant association with serum leptin values (R2 = 40.1%). Univariate and multivariate analyses using insulin resistance as the dependent variable showed that it had no association with leptin in both genders. Leptin had no correlation with proinsulin also. This study confirmed that in Asian Indians the association between plasma leptin and insulin concentrations is weak and that leptin has no influence on insulin resistance. Proinsulin and leptin are also not correlated in this population. Insulin resistance shows correlation with the beta-cell function both in men and women.     

Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells

Multiple myeloma (MM) is an incurable disease despite an initial response-rate of >60% with conventional or high-dose chemotherapy using glucocorticosteroids (i.e. dexamethasone), or alkylating agents (i.e. melphalan). Although these agents are capable of inducing complete remission (CR) in >50% of MM patients, resistance develops rapidly, in >90% of patients, within 2 years of treatment. Therefore, there is a need for new drugs for the treatment of relapsing and refractory MM patients. Gemcitabine (GEM) is a pyrimidine analog that blocks DNA synthesis, whereas, paclitaxel (TAX) is a mitotic spindle poison that promotes microtubular aggregation. Since it appears that these two drugs have different cellular targets, we examined the effect of each drug individually for several parameters and for possible synergy. We studied the cytotoxic effect of TAX and GEM on MM cells expressing varying levels of the antiapoptotic protein bcl-2, which is overexpressed in the majority of myeloma cell from MM patients. We found that both drugs are cytotoxic by inducing apoptosis, however, the extent of apoptosis with TAX, but not with GEM was dependent on the levels of bcl-2 expression. We further investigated the effect of TAX and GEM on the cell cycle distribution and on the levels of bcl-2. The results indicate that the two drugs have different modes of action with respect to each parameter tested. TAX induced arrest of the cells in the G2/M phase of the cell cycle, regardless of bcl-2 levels, however, apoptosis was induced in mitotic cells expressing relatively low levels of bcl-2. In contrast, GEM caused apoptosis of cells in the S-phase, regardless of level of bcl-2 expression. A major difference between TAX and GEM was in their effects on the levels of bcl-2. Whereas, TAX induced an early downregulation of bcl-2 (only in the cells with relatively low levels of bcl-2), treatment with GEM did not affect bcl-2 levels. The effects of TAX on both the cell cycle and bcl-2 were detected very early (4-8 h) and preceded the onset of apoptosis. GEM and TAX act synergistically, at low doses (IC50 of 0.5 microM for GEM and 0.025 microM for TAX), to effectively kill bcl-2 overexpressing cells that are resistant to higher doses (0.25 microM) of TAX alone. Therefore, we have initiated a phase II clinical trial of TAX and GEM for MM patients refractory to current therapy.     

Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome

The syndrome of insulin resistance comprises the following H-phenomena: 1. Hyperinsulinism compensating the inborn postreceptor insulin resistance, 2. Hyperglycaemia-non-insulin-dependent diabetes mellitus, 3. Hyperlipoproteinaemia with android obesity, 4. Hypertension, 5. Hirsutism with the syndrome of polycystic ovaries as a manifestation of a hyperandrogenic situation in the female organism. Molecular syndromes of this syndrome of insulin resistance are obscure. They are the subject of intensive studies because H-phenomena are an aggregation of the main risk factors of atherogenesis. Recently attention is focused also on amylin--a 37 amino acid peptide with a 50% homologous amino acid sequence with a calcitonin-gene--related peptide (CGRP), which is the product of a gene made up of three introns on the 12th chromosome. Amylin acts in the beta-cells of the pancreas as a co-secretion of insulin. If in excess, it is deposited in the form of an amyloid in the beta-cells. In the early stage of NIDDM it alters the physiological response of the beta-cell to glycaemic stimuli and food, in later stages of the disease, after accumulation, it causes apoptosis of the beta-cell and reduces thus the secretory capacity of the Langerhans islets. It is excreted in the urine and thus, if the glomerular filtration is reduced, it cumulates in the blood stream and thus enhances insulin resistance already in the early stages of chronic renal insufficiency, or in diabetic nephropathy. In type II diabetes similarly as insulin levels also amylin levels are elevated, while in type I diabetes with early autoimmune destruction of the beta-cells the insulin and amylin levels are reduced or even zero. Amylin reduces in the muscle, probably by inhibition of glycogen synthase, the insulin stimulated non-oxidative utilization of glucose into muscle glycogen and conversely by stimulation of phosphorylase it stimulates glycogenolysis and thus also lactate production and gluconeogenesis in the liver which all are anti-insulin effects which intensify the insulin resistance of the main target tissues. Amylin, similarly as CGRP or calcitonin, reduces Ca blood levels and has a vasodilatating effect; it reduces the BP but in different minimal and maximal doses and by a different mechanism and via special receptors because the link of amylin to calcitonin receptors is 100 times lower and does not produce a rise of cAMP in the target cell. The effect on the enhancement of insulin resistance in muscle was proved also by direct measurements using an hyperinsulinaemic euglycaemic clamp. After prolongation of the clamp to more than two hours the effect on insulin resistance disappeared, although the hypocalcinaemic effect persisted. Amylin is able by its biological action to modify the secretion as well as the effectiveness of insulin to pathological values. These two characteristics are typical for impaired glucose tolerance in type II diabetes. Studies are under way to find out whether the effect of amylin is involved directly also in the pathogenesis of the other H-phenomena or only via accentuation of hyperinsulinism. In any case amylin is a new link the role of which in the pathogenesis of NIDDM and the syndrome of insulin resistance awaits evaluation. Due to its effect on gastric evacuation it participates also in the postprandial glycaemic control in particular in type I diabetes where it it begins to be used in therapy. Perhaps it will be possible to administer it in these patients along with insulin to improve diabetes compensation.     

Stiffness indexes beta of the common carotid and femoral arteries are associated with insulin resistance in NIDDM

OBJECTIVE: To investigate the association between arterial wall stiffness indexes beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the diabetes center in Osaka City University Hospital, compared with 120 age- and sex-matched control subjects. Insulin sensitivity indexes were evaluated using a euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA and FA were significantly higher in NIDDM subjects than in control subjects (CCA 18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7 +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of diabetes, and mean blood pressure. In stepwise multiple regression analyses, insulin sensitivity index and duration of diabetes were identified as significant independent variables for stiffness indexes beta in both CCA and FA (CCA R2 = 0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.     

Mnemonic search, but not arithmetic transformation, is associated with psychophysiological inhibition.

The possibility that mnemonic search and arithmetic transformation induce transient heart rate (HR) slowing was studied. Transient HR slowing was assumed to result from the inhibition of premature responding during information processing. Twenty young men performed a 2-step reaction time task. Two precues were followed by a choice cue: 2 additional precues and 1 final choice cue. Choice cues were varied to compare spatial and perceptual-motor processing with mnemonic or arithmetic processing. Cardiac interbeat interval and impedance cardiograph measures were taken beat by beat. The preparation for the respond cue was associated with HR slowing followed by HR speeding associated with response initiation. Mnemonic search induced a transient HR slowing before the speeding initiated by the motor response. Arithmetic transformation did not, but processing of the arithmetic series decreased cue-induced transient HR slowing. Mnemonic search may be associated with a psychophysiological inhibition analogous to that observed in perceptual-motor tasks during response selection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance.     

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.     

Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer

BACKGROUND/AIMS: In planning adjuvant treatment of colorectal cancer, it is of critical importance to optimize the treatment by identifying subsets of patients that will respond or not to chemotherapy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are key enzymes involved in the biochemical functions of the antimetabolite 5-fluorouracil (5-FU). In searching for the factors determining the 5-FU sensitivity of colorectal cancer, TS and DPD were analyzed in relation to the inhibitory effect of 5-FU on cell proliferation in a series of human colorectal cancer cell lines. METHODOLOGY: TS and DPD protein expressions were quantified in 5 human colorectal cancer cell lines, using TS binding assay and Western blotting, respectively. Cellular growth inhibition was assessed by MTT assay after 48 hours of continuous exposure to 5-FU or cisplatin (CDDP). RESULTS: TS protein expression was detected in all but one of the cell lines studied and varied within a 17-fold range, while DPD protein expression was detectable in only one cell line (CaR1). CaR1, which expressed the highest level of DPD and no detectable TS, showed remarkable resistance to 5-FU. The other colorectal cancer cell lines with undetectable DPD expression were sensitive to 5-FU. There was no correlation between TS expression and 5-FU sensitivity. All of the cell lines studied showed similar sensitivity to CDDP. CONCLUSIONS: These data suggest that DPD, but not TS, expression predicts 5-FU sensitivity in colorectal cancer cell lines.     

Microalbuminuria, arterial hypertension and the cardiovascular risk

Both the Entamoeba histolytica lectin, a virulence factor for the causative agent of amebiasis, and the mammalian hepatic lectin bind to N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc. Polyvalent GalNAc-derivatized neoglycoproteins have >1000-fold enhanced binding affinity for both lectins (Adler,P., Wood,S.J., Lee,Y.C., Lee,R.T., Petri,W.A.,Jr. and Schnaar,R.L.,1995, J. Biol. Chem ., 270, 5164-5171). Substructural specificity studies revealed that the 3-OH and 4-OH groups of GalNAc were required for binding to both lectins, whereas only the E.histolytica lectin required the 6-OH group. Whereas GalNAc binds with 4-fold lower affinity to the E.histolytica lectin than to the mammalian hepatic lectin, galactosamine and N-benzoyl galactosamine bind with higher affinity to the E. histolytica lectin. Therefore, a synthetic scheme for converting polyamine carriers to poly-N-acyl galactosamine derivatives (linked through the galactosamine primary amino group) was developed to test whether such ligands would bind the E.histolytica lectin with high specificity and high affinity. Contrary to expectations, polyvalent derivatives including GalN6lys5, GalN4desmosine, GalN4StarburstTMdendrimer, and GalN8StarburstTMdendrimer demonstrated highly enhanced binding to the mammalian hepatic lectin but little or no enhancement of binding to the E.histolytica lectin. We propose that the mammalian hepatic lectin binds with greatest affinity to GalNAc "miniclusters," which mimic branched termini of N-linked oligosaccharides, whereas the E.histolytica lectin binds most effectively to "maxiclusters," which may mimic more widely spaced GalNAc residues on intestinal mucins.     

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary.     

Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome

Genetic variation in the APOE gene and variation in chromosome 21 genotypes, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudinal neuropsychological analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/- 1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype distributions were compared among subgroups with or without evidence of cognitive decline. Genetic variability at APOE and APP was not significantly associated with evidence of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic variability at D21S11. These findings are discussed in the context of current hypotheses of Alzheimer-type dementia in Down syndrome and in the general population.     

Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM

In an attempt to identify the genetic basis for susceptibility to non-insulin-dependent diabetes mellitus within the context of obesity, we generated 401 genetically obese Leprfa/Leprfa F2 WKY13M intercross rats that demonstrated wide variation in multiple phenotypic measures related to diabetes, including plasma glucose concentration, percentage of glycosylated hemoglobin, plasma insulin concentration, and pancreatic islet morphology. Using selective genotyping genome scanning approaches, we have identified three quantitative trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2 progeny demonstrated sexual dimorphism for these traits, with increased diabetes susceptibility in the males appearing at approximately 6 weeks of age, as sexual maturation occurred. For each of the QTLs, the linked phenotypes demonstrated sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a region vicinal to that previously linked to adiposity in studies of diabetes susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely related to the Wistar counterstrain we employed. Several candidate genes, including tubby (tub), multigenic obesity 1 (Mob1), adult obesity and diabetes (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous to the QTL region identified on rat Chr. 1.     

Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome

For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.     

Globus sensation is associated with hypertensive upper esophageal sphincter but not with gastroesophageal reflux

Globus sensation (globus) is best described as a constant feeling of a lump or fullness in the throat. Although the etiology of globus remains unclear, it has been attributed to a hypertensive upper esophageal sphincter (UES) resting pressure and to gastroesophageal reflux (GER). The aim of this study was, therefore, to determine if significant associations existed among globus, UES resting pressure, and GER. We reviewed the records of all patients who had stationary esophageal manometry over a 21/2-year interval with specific attention to symptoms of globus, UES pressures, and ambulatory pH studies. Patients with hypotensive UES (<30 mm Hg) were excluded. Chi square (chi2) test was used to determine significant associations. Six hundred fifty patients had normal UES resting pressures and 101 patients had hypertensive UES (>118 mm Hg). Seventeen of the 650 (3%) (16 women/1 man; mean age: 48, range 32-81 years) with normal UES described globus. Conversely, 28 of the 101 (28%) (15 women/13 men; mean age: 43, range 23-61 years) patients with hypertensive UES described globus. There was a significant association between hypertonicity of the UES and globus (chi2=93.42, P < 0.0001). In patients with normal UES, globus occurred predominantly in females (chi2=6.33, P < 0.01). Twenty-three (16 women/7 men; mean age: 43, range 23-60 years) of the 45 patients with globus had prior ambulatory pH studies. Six of 23 (26%) had GER. Compared to an age-, sex-, and UES-pressure-matched group of 23 patients (16 women/7 men; mean age: 44, range 22-75 years) without globus, nine (39%) had GER, thus showing no significant association of globus with GER (P=0.35). There also was no significant association of GER with normal UES or with hypertensive UES in these patients. In conclusion, there is a significant association between hypertensive UES and globus. The data suggest two possible etiologies: female patients with normal UES pressure potentially having increased afferent sensation and a group with equal sex distribution but abnormally elevated UES resting pressure. This study does not support GER as an etiology of globus.     

Influence of aging on progression of cardiovascular complications associated with insulin resistance in patients with essential hypertension

A simplified method of diagnosing anterior divisional blocks (hemiblocks) at a glance is made possible by using a knowledge of the lead line directions on a hexaxial system. The term 'divisional block' is preferred to 'hemiblock' because a block of one of the three divisions of the left bundle cannot be a hemiblock. The diagnosis of an anterior divisional block can be simplified by utilization of the concept that it is mainly a terminal conduction abnormality in the frontal plane with a direction between -60 degree and -90 degree. Using a hexaxial system the diagnosis can be quickly made regardless of axis by simply noting the presence of a terminal negativity (S wave) in aVF, terminal positivity in aVR (R or R'), and no S in lead 1.     

Female sex is associated with increased mortality and morbidity early, but not late, after coronary artery bypass grafting

OBJECTIVE: To describe mortality and morbidity during a period of 2 years after coronary artery bypass grafting in relation to gender. DESIGN: Prospective follow-up study. SETTING: Two regional cardiothoracic centres which performed all the coronary artery bypass operations in western Sweden at the time. SUBJECTS: A total of 2129 (1727 (81%) men and 402 (19%) women) consecutive patients undergoing coronary artery bypass surgery between June 1988 and June 1991 without concomitant procedures. RESULTS: Females were older and more frequently had a history of hypertension, diabetes mellitus, congestive heart failure, renal dysfunction and obesity. In a multivariate analysis, taking account of age, history of cardiovascular diseases and renal dysfunction, female sex appeared as a significant independent predictor of mortality during the 30 days after coronary artery bypass grafting (P < 0.05), but not thereafter. Various postoperative complications including neurological deficit, hydro- and pneumo-thorax, perioperative myocardial damage and the need for assist devices and prolonged reperfusion were more common in females than males. CONCLUSION: Females run an increased risk of early death and the development of postoperative complications after coronary artery bypass surgery as compared with males. Late mortality does not appear to be influenced by gender and the long-term benefit of the coronary artery bypass graft operation is similar in men and women.