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Vaughan, Carl J., Anna M. Aherne, Eamon Lane, Orla Power, Robert M. Carey, and Damian P. O'connell. Identification and regional distribution of the dopamine [D.sub.1A] receptor in the gastrointestinal tract. Am J Physiol Regulatory Integrative Comp Physiol 279: R599-R609, 2000.--Dopamine (DA) is regarded as an important modulator of enteric function. Recent experiments have suggested that newly cloned DA receptor subtypes are widely expressed in peripheral organs, including the gastrointestinal tract. In the present studies, the [D.sub.1A] receptor subtype was identified in rat gut regions through localization of receptor protein by means of light microscopic immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in situ amplification and hybridization (3SR in situ). [D.sub.1A] receptor immunoreactivity was shown to have a diverse distribution in the gastrointestinal tract, being present in the gastroesophageal junction, stomach, pylorus, small intestine, and colon. The receptor has a transmural distribution present in both epithelial and muscle layers as well as in blood vessels and lamina propria cells of different gastrointestinal regions. Western blot analysis demonstrated a single 50-kDa band for esophagus, stomach, duodenum, jejunum, and colon. The in situ hybridization signal was localized to the same sites revealed by [D.sub.1A] receptor immunoreactivity. RT-PCR revealed an appropriate sized signal in similar regions. This study is the first to identify expression of the central [D.sub.1A] receptor throughout the normal mammalian gastrointestinal tract. immunohistochemistry; messenger ribonucleic acid

A 22-year-old woman was referred with exertional dyspnoea and chest tightness 3weeks following a diagnosis of COVID-19. Evaluation revealed a resting sinus tachycardia and criteria for postural orthostatic tachycardia syndrome were met. After non-pharmacological interventions failed to yield symptomatic improvement, ivabradine was commenced. This intervention was followed by a substantial improvement in the patient’s exercise tolerance and energy levels and an objective reduction in supine and standing heart rate. [ABSTRACT FROM AUTHOR]

The authors deal with common coronary anomalies, discuss their anatomy and some diagnostic and clinical aspects, and describe some of the principles of management. [ABSTRACT FROM PUBLISHER]

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1α of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a+/- mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a+/- mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a+/- mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation. [ABSTRACT FROM AUTHOR]

PRKAG2 Gene in Sporadic WPW Syndrome. Introduction: Mutations in the PRKAG2 gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase have been shown to cause autosomal dominant Wolff-Parkinson-White (WPW) syndrome associated with hypertrophic cardiomyopathy. Prior studies focused on familial WPW syndrome associated with other heart disease such as hypertrophic cardiomyopathy. However, such disease accounts for only a small fraction of WPW cases, and the contribution of PRKAG2 mutations to sporadic isolated WPW syndrome is unknown. Methods and Results: Subjects presented for clinical electrophysiologic evaluation of suspected WPW syndrome. WPW syndrome was diagnosed by ECG findings and/or by clinically indicated electrophysiologic study prior to enrollment. Echocardiography excluded hypertrophic cardiomyopathy. Denaturing high-performance liquid chromatography and automated sequencing were used to search for PRKAG2 mutations. Twenty-six patients without a family history of WPW syndrome were studied. No subject had cardiac hypertrophy, and only one patient had associated congenital heart disease. Accessory pathways were detected at diverse locations within the heart. Two polymorphisms in PRKAG2 were detected. [inv6+36insA] occurred in intron 6 in 4 WPW patients and [inv10+10delT] in intron 10 in 1 WPW patient. Both occurred in normal unrelated chromosomes. No PRKAG2 mutations were detected. Conclusion: This study shows that, unlike familial WPW syndrome, constitutional mutation of PRKAG2 is not commonly associated with sporadic WPW syndrome. Although polymorphisms within the PRKAG2 introns were identified, there is no evidence that these polymorphisms predispose to accessory pathway formation because their frequency is similarly high in both WPW patients and normal individuals. Further studies are warranted to identify the molecular basis of common sporadic WPW syndrome.(J Cardiovasc Electrophysiol, Vol. 14, pp. 263-268, March 2003). [ABSTRACT FROM AUTHOR]

Offers information on the proper selection of 6 HMG-CoA reductase inhibitors or statins for the treatment of hypercholesterolemia. Statins available in the market; Similarity of the mechanisms of action; Ability to lower low density lipoprotein cholesterol levels in the blood; Value of statin therapy; Differences in potency based on maximum approved dosages.

Determines the regional distribution of the D[sub 1A] receptor throughout the rat gastrointestinal tract (GIT). Light microscopic immunohistochemistry; In situ amplification and hybridization histochemistry.

Presents several letters to the editors of "Lancet" and responses. Findings of the Heart Protection Study (HPS) which found that therapy with simvastatin reduced the composite primary endpoint of coronary heart disease (CHD) death; Discovery that tamoxifen may not significantly reduce the rate of breast cancer in women who have had hysterectomies; Effect of diet on blood pressure; Concerns over the high rate of HIV/AIDS in Africa; Focus on HIV-1 incidence and prevalence in Uganda; Efforts to control HIV/AIDS in India; Update from Mbarara University Teaching Hospital in Uganda; The connection between human pituitary growth hormone and risk of developing cancer; Method of relieving benign paroxysmal positional vertigo which developed following a trip on a roller coaster.