Adenylate cyclase: Its probable localization in sarcoplasmic reticulum as well as sarcolemma of the canine heart

Cardiac microsomes prepared by two different methods were compared in terms of Ca-binding and Ca-uptake, believed to represent markers for fragmented sarcoplasmic reticulum, and the (Na⁺ + K⁺)-activated ATPase activity considered to be a marker for the plasma membrane. Microsomes prepared in dilute buffer (H₂O-microsomes) contain two to four times the activity of sarcoplasmic reticulum markers when compared to microsomes prepared in 10% sucrose (suc-microsomes). Conversely, the plasma membrane marker was present in greater amounts in the suc-microsomes. Basal, epinephrine-stimulated and NaF-stimulated adenylate cyclase activities were slightly higher in H₂O-microsomes, as was the degree of stimulation by the β-adrenergic agonist. These findings provide evidence that both β-receptor and adenylate cyclase activities may be present in the heart's sarcoplasmic reticulum, as well as in the sarcolemma.     

Using an office system intervention to increase breast cancer screening

OBJECTIVE: To evaluate an innovative approach to continuing medical education, an outreach intervention designed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practices. DESIGN: Randomized, controlled trial with primary care practices assigned to either the intervention group or control group, with the practice as the unit of analysis. SETTING: Twenty mostly rural counties in North Carolina. PARTICIPANTS: Physicians and staff of 62 randomly selected family medicine and general internal medicine practices, primarily fee-for-service, half group practices and half solo practitioners. INTERVENTION: Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance, and to assist these primary care practices in developing office systems tailored to increase breast cancer screening. MEASUREMENTS AND MAIN RESULTS: Physician questionnaires were obtained at baseline and follow-up to assess the presence of five indicators of an office system. Three of the five indicators of office systems increased significantly more in intervention practices than in control practices, but the mean number of indicators in intervention practices at follow-up was only 2.8 out of 5. Cross-sectional reviews of randomly chosen medical records of eligible women patients aged 50 years and over were done at baseline (n=2,887) and follow-up (n=2,874) to determine whether clinical breast examinations and mammography, were performed. Results for mammography were recorded in two ways, mention of the test in the visit note and actual report of the test in the medical record. These reviews showed an increase from 39% to 51% in mention of mammography in intervention practices, compared with an increase from 41% to 44% in control practices (p=.01). There was no significant difference, however, between the two groups in change in mammograms reported (intervention group increased from 28% to 32.7%; control group increased from 30.6% to 34.0%, p=.56). There was a nonsignificant trend (p=.06) toward a greater increase in performance of clinical breast examination in intervention versus control practices. CONCLUSIONS: A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography, but had little impact on actual performance of breast cancer screening. At follow-up, few practices had a complete office system for breast cancer screening. Outreach approaches to assist primary care practices implement office systems are promising but need further development. Presented in part at the 19th annual meeting of the Society of General Internal Medicine, Washington, DC, May 1996. This research was supported under grant CA 54343-02 from the National Cancer Institute.     

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.     

Implementing Point-of-Care Troponin Testing in the Emergency Department: Impact on Time to Result

IntroductionIn the emergency department, troponin assays are commonly used and essential in the evaluation of chest pain and diagnosis of acute coronary syndrome. This study was designed to assess the potential impact of implementing point-of-care troponin testing by comparing the time to point-of-care laboratory result and time to conventional laboratory result.MethodsThe study enrolled 60 ED patients deemed to need a troponin test in the evaluation of low-risk chest pain (HEART score <4 based on history, electrocardiogram, age, risk factors). Point-of-care troponin testing was performed with the same blood sample obtained for a conventional troponin assay. If the provider determined that the patient required 2 troponin tests, the second laboratory draw was used in the data collection. This was to correlate the time of laboratory result to time of disposition.ResultsOf the 60 subjects enrolled, 2 subjects were excluded because of user errors with the point-of-care testing equipment and 2 others for not meeting inclusion criteria on later review. The median times for the point-of-care troponin and conventional troponin assays were 11:00 minutes (interquartile range 10:00-15:30) and 40:00 minutes (interquartile range 31:30-52:30), respectively; P < 0.001. There were 3 extreme outliers from the conventional troponin assay that significantly skewed the distribution of the mean, making the median the more accurate assessment of the central tendency.DiscussionPoint-of-care troponin testing provided results in a median time 29 minutes quicker than the conventional troponin assay. This result is statistically significant and has the potential to greatly improve time to disposition in all patients with chest pain requiring a troponin assay.     

A serotonin hypothesis of schizophrenia

Chronic widespread stress-induced serotonergic overdrive in the cerebral cortex in schizophrenia, especially in the anterior cingulate cortex (ACC) and dorsolateral frontal lobe, is the basic cause of the disease. The concept of excessive serotonergic stimulation is supported by NMR spectroscopy; peripheral depletion of phospholipids, serotonergic 5-HT_2A receptors being linked to phospholipase A₂; positron emission tomography data with serotonergic ligands; and the fact that blockade of serotonergic 5-HT_2A receptors by atypical neuroleptics slows down the course of the disease. Disruption of glutamate signalling by serotonergic overdrive leads to neuronal hypometabolism and ultimately synaptic atrophy and grey matter loss according to principles of brain plasticity. Normal dopamine input to an impaired ACC causes positive symptoms. Frontal lobe hibernation causes negative symptoms and cognitive impairment.     

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

     

Small body size of pseudoscorpions and a distinct architecture of the ovary: A step to miniaturization?

Chelicerata, the second largest subphylum of Arthropoda, includes invertebrates with a wide range of body size. Pseudoscorpions are among small or miniature chelicerates which exhibit several morphological, anatomical, and developmental features related to miniaturization, e.g., replacement of book lungs by tracheae, unpaired gonads, and matrotrophic development of the embryos outside the female body, in the brood sac. In this paper, we show the ovary structure of two pseudoscorpion species, Cheiridium museorum and Apocheiridium ferum (Cheiridiidae). Both cheiridiids are one of the smallest pseudoscorpions. The results of our observations conducted in light, transmission electron, and confocal microscopy demonstrate that the ovary of C. museorum and A. ferum, displays a significant structural difference that is unusual for chelicerates. The difference concerns the spatially restricted position of the germarium. We show that such ovary architecture results in a significantly reduced number of growing oocytes and in consequence a reduced number of deposited eggs. A centrally located germarium implies also a modified pattern of ovary development during oocyte growth due to long distance migration of the germline and the accompanying somatic cells. Herein, we postulate that such an ovary structure is related to the pseudoscorpion's small body size and it is a step towards miniaturization in the smaller pseudoscorpions species.