Natural history of frozen shoulder: fact or fiction? A systematic review.

BACKGROUND: In 1940s, it was proposed that frozen shoulder progresses through a self-limiting natural history of painful, stiff and recovery phases, leading to full recovery without treatment. However, clinical evidence of persistent limitations lasting for years contradicts this assumption. OBJECTIVES: To assess evidence for the natural history theory of frozen shoulder by examining: (1) progression through recovery phases, and (2) full resolution without treatment. DATA SOURCES: MEDLINE, PubMed, EBSCO CINAHL and PEDro database searches augmented by hand searching. STUDY SELECTION: Cohort or randomised controlled trials with no-treatment comparison groups including adults with frozen shoulder who received no treatment and reporting range of motion, pain or function for ≥6 months. DATA EXTRACTION: Reviewers assessed study eligibility and quality, and extracted data before reaching consensus. Limited early range-of-motion improvements and greater late improvements defined progression through recovery phases. Restoration of normal range of motion and previous function defined full resolution. RESULTS: Of 508 citations, 13 articles were reviewed and seven were included in this review. Low-quality evidence suggested that no treatment yielded some, but not complete, improvement in range of motion after 1 to 4 years of follow-up. No evidence supported the theory of progression through recovery phases to full resolution without treatment. On the contrary, moderate-quality evidence from three randomised controlled trials with longitudinal data demonstrated that most improvement occurred early, not late. LIMITATIONS: Low-quality evidence revealed the weakness of longstanding assumptions about frozen shoulder. CONCLUSION: Contradictory evidence and a lack of supporting evidence shows that the theory of recovery phases leading to complete resolution without treatment for frozen shoulder is unfounded.

Properties, expression and potential roles of cardiac K+ channel accessory subunits: MinK, MiRPs, KChIP, and KChAP.

Over the past 10 years, cDNAs encoding a wide range of pore-forming K(+)-channel alpha-subunits have been cloned and found to result in currents with many properties of endogenous cardiac K(+) channels upon homomeric expression in heterologous systems. However, a variety of remaining discrepancies have led to a search for other subunits that might be involved in the formation of native channels. Over the past few years, a series of accessory subunits has been discovered that modify current properties upon coexpression with alpha-subunits. One of these, the minimal K(+)-channel subunit minK, is essential for formation of the cardiac slow delayed-rectifier K(+) current, I(Ks), and may also interact in functionally important ways with other alpha-subunits. Another, the K(+)-channel interacting protein KChIP appears critical in formation of native transient outward current (I(to)) channels. The roles of 2 other accessory subunits, the minK-related peptide MiRP and the K(+)-channel accessory protein, KChAP, remain unclear. This article reviews the available knowledge regarding the accessory subunits minK, MiRP, KChIP and KChAP, dealing with their structure, effects on currents carried by coexpressed alpha-subunits, expression in cardiac tissues and potential physiological function. On the basis of the available information, we attempt to assess the potential involvement of these accessory K(+)-channel subunits in cardiac pathophysiology and in developing new therapeutic approaches.

Arrhythmogenic ionic remodeling: adaptive responses with maladaptive consequences.

Compensatory changes in ion transport mechanisms occur in response to a variety of cardiac disease processes. Recent work has demonstrated that these adaptive responses can produce the arrhythmogenic substrate for a variety of important cardiac rhythm disorders. Two important paradigms are atrial tachycardia-induced remodeling and ionic remodeling caused by congestive heart failure. Atrial tachycardia promotes cellular Ca(2)+ loading and downregulates a variety of ion channels, particularly L-type Ca(2)+ channels, thereby promoting the occurrence and maintenance of atrial fibrillation. Congestive heart failure alters the expression and function of a variety of membrane transport processes, including several K(+)-channels and key Ca(2)+-transport systems, favoring the occurrence of arrhythmogenic afterdepolarizations. An improved understanding of the mechanisms and consequences of arrhythmogenic ionic remodeling promises to lead to novel and improved therapeutic approaches.

Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart.

Five isoforms of the muscarinic acetylcholine receptor (mAChR) have been identified by molecular cloning and designated m(1)-m(5), of which four correspond to the functional subtypes M(1), M(2), M(3), and M(4) in primary tissues. The presence of M(5) receptors in tissues remains uncertain. The present study was designed to explore the diversity and cellular distribution of various mAChR subtypes in human hearts. Competition binding of [N-methyl-(3)H]-scopolamine methyl chloride with various mAChR antagonists yielded data consistent with the presence of multiple subtypes (M(1)/M(2)/M(3)/M(5)) of mAChRs in both human atrial (HA) and ventricular (HV) tissues. Expression of mRNAs encoding all five subtypes was readily detected by reverse transcription-polymerase chain reaction in both HA and HV samples. Immunoblotting with subtype-specific antibodies confirmed the presence of M(1), M(2), M(3), and M(5), but not M(4), proteins in membrane preparations from both HA and HV. The protein levels of M(1) and M(2) were comparable between HA and HV. Although the density of M(3) appeared approximately 10-fold higher in HV than HA, that of M(5) was approximately 5 times lower in HV than in HA. Positive immunostaining of single ventricular myocytes by M(1), M(2), M(3), and M(5) antibodies, respectively, was consistently detected. Under confocal microscopy, M(5) showed characteristic localization to the intercalated discs, whereas other subtypes were more evenly distributed throughout the surface membrane. Our results provide the first molecular evidence for the presence of multiple subtypes of mAChR, including endogenous M(5) receptors, in human hearts and suggest that different subtypes have different tissue distributions and cellular localization.