Serum high density lipoprotein cholesterol correlates with presence but not severity of coronary artery disease

An elevated serum level of low density lipoprotein (LDL) is a risk factor for the development of coronary artery disease, whereas elevated levels of high density lipoprotein (HDL) appear to have a protective effect, and the total cholesterol to HDL ratio has been suggested as an improved method for assessing risk. We determined cholesterol, HDL and triglycerides in 189 patients undergoing diagnostic cardiac catheterization to determine if these variables correlate with the severity of coronary artery disease assessed as the number of major coronary vessels having ≥ 70 percent stenosis. HDL was higher in the group with zero vessel disease (54 ± 2.3 mg/dl ± SEM) than in those with one, two or three vessel disease (43 ± 1.8, 45 ± 1.8 and 51 ± 1.2, respectively), and the cholesterol to HDL ratio was lower in the group with zero vessel disease (4.1 ± 0.2 compared to 6.1 ± 0.3, 5.7 ± 0.2 and 6.4 ± 0.3 in the groups with 1, 2 and 3 vessel disease).Using analysis of variance, patients with no coronary artery disease (zero vessel disease) differed from those with coronary artery disease in HDL (p < 0.005), triglycerides (p > 0.01), cholesterol (p < 0.005) and cholesterol to HDL (p > 0.005), but no significant differences were found between patients with coronary artery disease and a different number of vessels involved. There were no significant differences between the groups in age, and although the group with zero vessel disease had more females than the others, there were no differences in cholesterol, HDL, cholesterol to HDL ratio, or triglycerides between male and female patients with no coronary artery disease. We conclude that the cholesterol to HDL ratio correlates with the presence but not severity of coronary artery disease.     

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Risk for emerging bipolar disorder,variants, and symptoms in children with attention deficit hyperactivity disorder,now grown up

AIM: To determine the prevalence of bipolar disorder (BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder (ADHD) through 14 years’ follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type I and II diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD (MTA). We used the diagnostic interview schedule for children (DISC), administered to both parents (DISC-P) and youth (DISCY). We compared the MTA study subjects with ADHD (n = 579) to a local normative comparison group (LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts (TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic (PM) and non-specific manic (NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD (1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time (df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability (BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG (χ² = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM (df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2 (A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.     

A quantitative real-time RT-PCR assay for salmon IGF-I mRNA, and its application in the study of GH regulation of IGF-I gene expression in primary culture of salmon hepatocytes

The hormone insulin-like growth factor-I (IGF-I) regulates vertebrate growth. The liver produces most circulating IGF-I, under the control of pituitary growth hormone (GH) and nutritional status. To study the regulation of liver IGF-I production in salmon, we established a primary hepatocyte culture system and developed a TaqMan quantitative real-time RT-PCR assay for salmon IGF-I gene expression. A portion of the coho salmon acidic ribosomal phosphoprotein P0 (ARP) cDNA was sequenced for use as a reference gene. A systematic bias across the 96 well PCR plate was discovered in an initial IGF-I assay, which was corrected when the assay was redesigned. IGF-I mRNA levels measured with the validated assay correlated well with levels measured with an RNase protection assay, and were highest in liver compared with other tissues. We examined the time course of hepatocyte IGF-I gene expression over 48 h in culture, the response to a range of GH concentrations in hepatocytes from fed and fasted fish, and potential effects of variation in IGF-I in the medium. IGF-I gene expression decreased over time in culture in hepatocytes in plain medium, and in cells treated with 5 nM GH with or without a combination of metabolic hormones (1 microM insulin, 100 nM triiodothyronine, and 0.1 nM dexamethasone). GH stimulated IGF-I gene expression at all time points. In cells treated with GH plus metabolic hormones, IGF-I gene expression was intermediate between the controls and GH alone. Increasing concentrations of GH resulted in biphasic IGF-I gene expression response curves in cells from fed and fasted fish, with the threshold for stimulation from 0.5 to 2.5 nM GH, maximal response from 5 to 50 nM, and a reduced response at 500 nM. Medium IGF-I (5 nM) did not affect basal or GH stimulated IGF-I gene expression. This study shows that primary hepatocyte culture and the TaqMan IGF-I assay can be used to study the regulation of hepatic IGF-I gene expression in salmon, and provides the first evidence of a biphasic response to GH concentration in fish hepatocyte culture.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Bile duct antibodies crossreacting with blood group antigens in primary sclerosing cholangitis.

Indirect immunoperoxidase histochemistry was used to localise and determine the disease, species, and tissue specificity of bile duct antibodies in primary sclerosing cholangitis. Serum was collected from: 29 patients with primary sclerosing cholangitis, 18 patients with ulcerative colitis alone, 19 patients with extrahepatic biliary obstruction of other causes, and 42 healthy control subjects. Bile duct antibodies reacted with an antigen localised to the small and large intrahepatic bile ducts. When blood group A human liver was used they were detected in 34% of patients with primary sclerosing cholangitis. They were not detected when blood group O human liver was used. Bile duct antibodies that reacted with obstructed and normal rabbit liver were detected in 34% and 17% respectively of patients with primary sclerosing cholangitis but were also present in similar proportions of control subjects. Colon antibodies that reacted with human and rabbit colon were found in 52% and 24% respectively of patients with primary sclerosing cholangitis. Absorption studies using blood group substances A and B abolished the reactivity of bile duct antibodies with human and rabbit liver and that of colon antibodies' with rabbit colon. Colon antibodies that reacted with human colon were not absorbed. Absorption studies using isolated peripheral white blood cells did not affect reactivity of bile duct or colon antibodies. We conclude that bile duct antibodies are disease, species, and tissue non-specific and react with blood group A/B antigens present in human and rabbit bile ducts and rabbit colon. This suggests that they do not play a role in the pathogenesis of primary sclerosing cholangitis.     

Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study

The distribution of corticotropin-releasing factor (CRF)-immunoreactive cells and fibers has been examined in the brains of normal adult rats, and in the brains of animals that had been pretreated with intraventricular injections of colchicine, or had been adrenalectomized 3-60 days before perfusion. The results suggest that CRF immunoreactivity is localized in at least three functionally distinct systems. First, most of the CRF-stained fibers in the neurohemal zone of the median eminence, which presumably modulate the release of ACTH and beta-endorphin from the pituitary, appear to arise in the paraventricular nucleus of the hypothalamus (PVH). About 2,000 CRF-stained cells are distributed throughout all eight parts of the PVH, although a majority (80%) of the cells are concentrated in the parvocellular division, and a smaller number (about 15%) are found in parts of the magnocellular division in which oxytocinergic cells predominate. This appears to be the only CRF-stained pathway in the brain that is affected (increased staining intensity) by adrenalectomy. Second, a series of cell groups in the basal telencephalon, hypothalamus, and brain stem that are known to play a role in the mediation of autonomic responses contain CRF-stained neurons. These areas, which are interconnected by stained fibers in the medial forebrain bundle and the periventricular system, include the central nucleus of the amygdala, substantia innominata, bed nucleus of the stria terminalis, medial and lateral preoptic areas, lateral hypothalamic area, central gray, laterodorsal tegmental nucleus, locus ceruleus, parabrachial nucleus, dorsal vagal complex, and regions containing the A1 and A5 catecholamine cell groups. And third, scattered CRF-stained cells are found throughout most areas of the cerebral cortex. Most such cells are confined to layers II and III in the neocortex, and their bipolar shape suggests that they are interneurons. These cells are most common in limbic regions including prefrontal areas, the cingulate gyrus, and areas bordering the rhinal fissure. Scattered immunoreactive cells are also found in dorsal parts of the dentate gyrus and Ammon's horn. These results suggest that the PVH plays a critical role in the modulation of ACTH and beta-endorphin release from the pituitary, and that CRF-containing pathways in the brain are involved in the mediation of autonomic responses.