Metabolic panniculitis: alpha‐1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Panniculitis can be the initial presentation of both alpha‐1 antitrypsin deficiency and pancreatic disease. They can both present with abscess‐like draining nodules, but may present like other forms of panniculitis with erythematous nodules. It is important to consider these in the differential diagnosis of patients presenting with panniculitis. Alpha‐1 antitrypsin deficiency is a relatively common disorder mainly affecting the lungs and liver. It frequently goes undiagnosed, yet critical interventions can be made to minimize disease progression. Panniculitis associated with alpha‐1 antitrypsin deficiency can be difficult to treat. Pancreatic panniculitis occurs in less than 3% of patients with underlying pancreatic disease and is often associated with arthritis. Diagnosis and treatment of the underlying pancreatic disease is imperative.     

Acquired erythroderma in adults: a clinical and prognostic study

Background Erythroderma is a severe syndrome and prognostic studies are rare in the literature. Objectives Through a retrospective study of erythroderma in adults, we have analysed epidemiological and clinical data and precised the relevant aetiologies and survival in our patients. Methods This study was performed at the Department of Dermatology of Charles Nicolle Hospital of Tunis (1995–2007) including 82 cases of acquired erythroderma (>16 years). We have recorded epidemio‐clinical, biological and histological data, treatment and outcome. Clinical–histological correlation was analysed [kappa coefficient (κ)]. Follow‐up time and disease‐free survival time were calculated as were Kaplan–Meier estimates of overall survival and relapse‐free survival for some aetiologies. Results Erythroderma represented 0.44‰ of all dermatoses with an age of 55.13 ± 18.16 and no sex predilection. Psoriasis was the predominant aetiology (32.9%) with a median duration of 6.75 years and previous one or more episodes of erythroderma. Psoriasis was significantly associated with pruritus (P = 0.0001), pachyonychia (P = 0.00001), palmoplantar keratoderma (P = 0.0001) and hypereosinophilia (P = 0.008). The latter is then not specific for drug induced erythroderma (P = 0.004). Carbamazepine (27.8%) and penicillin (22.2%) were the most implicated drugs. Positive Clinical–histological correlation was found in 77% of cases (κ = 0.753). Relapse was seen in all aetiologies, but drug reactions and had occurred in the first 3 years in 90% of them. Mortality rate was 11.3 per 1000 patients‐years. Conclusions Our study illustrates the severity of erythroderma. It alters heavily the quality of life of patients which is initially altered by the pre‐existent dermatosis. It may be life threatening as mortality rate is high.     

Acute non-Q wave cocaine-related myocardial infarction

Since our initial report in 1984 of six patients with AMI temporally related to cocaine use, we have observed 19 additional patients in whom ischemic chest pain syndromes occurred shortly after intranasal or IV use of cocaine or after smoking the drug. Seventeen patients (89 percent) developed non-Q wave infarction and two had Q-wave infarction. One patient manifested angina with striking ST-segment elevation. None of the patients had diabetes or hypertension, and all but one were cigarette smokers. The serum cholesterol level was 162 +/- 7 mg/dl. Four of the five patients who consented to coronary angiographic studies displayed normal coronary arteries, and one showed proximal stenosis of the right coronary artery. The cold pressor test was performed in seven patients; none had angina or ECG changes induced by cold stimulation. We conclude that T-wave infarction is a common form of an acute cardiac event related to cocaine abuse, and its pathogenesis may involve that of the cocaine-induced coronary vasospasm.     

Insulin resistance and the endothelium

There is increasing evidence of a parallel progression between insulin resistance and endothelial dysfunction, suggesting a close association between insulin action and the endothelium. Numerous studies have demonstrated that endothelial dysfunction occurs early in the insulin-resistant state and is predictive of future cardiovascular events. Similarly, insulin resistance has been associated with the metabolic syndrome, which also increases the risk of adverse cardiovascular outcomes. Approaches that improve endothelial dysfunction, such as treatment with statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or peroxisome proliferator-activated receptor gamma ligands, have been shown to prevent both diabetes and cardiovascular disease. This article reviews the relation between endothelial dysfunction and cardiovascular disease, assesses the endothelium in the spectrum of insulin resistance, and examines the effect of the thiazolidinediones on endothelial function.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

Evaluation of Hybridization Capture Versus Amplicon‐Based Methods for Whole‐Exome Sequencing

Next‐generation sequencing has aided characterization of genomic variation. While whole‐genome sequencing may capture all possible mutations, whole‐exome sequencing remains cost‐effective and captures most phenotype‐altering mutations. Initial strategies for exome enrichment utilized a hybridization‐based capture approach. Recently, amplicon‐based methods were designed to simplify preparation and utilize smaller DNA inputs. We evaluated two hybridization capture‐based and two amplicon‐based whole‐exome sequencing approaches, utilizing both Illumina and Ion Torrent sequencers, comparing on‐target alignment, uniformity, and variant calling. While the amplicon methods had higher on‐target rates, the hybridization capture‐based approaches demonstrated better uniformity. All methods identified many of the same single‐nucleotide variants, but each amplicon‐based method missed variants detected by the other three methods and reported additional variants discordant with all three other technologies. Many of these potential false positives or negatives appear to result from limited coverage, low variant frequency, vicinity to read starts/ends, or the need for platform‐specific variant calling algorithms. All methods demonstrated effective copy‐number variant calling when evaluated against a single‐nucleotide polymorphism array. This study illustrates some differences between whole‐exome sequencing approaches, highlights the need for selecting appropriate variant calling based on capture method, and will aid laboratories in selecting their preferred approach.     

Kinesio Tape and Shoulder-Joint Position Sense

Context

Joint position sense (JPS) is a key neuromuscular factor for developing and maintaining control of muscles around a joint. It is important when performing specialized tasks, especially at the shoulder. No researchers have studied how Kinesio Tape (KT) application affects JPS.

Objective

To investigate the effects of KT application and no tape on shoulder JPS at increasing shoulder elevations in athletes.

Design

Cross-sectional study.

Setting

University laboratory.

Patients or Other Participants

A total of 27 healthy athletes who did not participate in overhead sports (age = 20.44 ± 1.05 years, height = 175.02 ± 11.67 cm, mass = 70.74 ± 9.65 kg) with no previous pathologic shoulder conditions volunteered for the study. All participants were from 1 university.

Intervention(s)

Shoulder JPS was assessed at increasing elevations with and without KT application. Participants attempted to actively replicate 3 target positions with and without the KT and without visual guidance.

Main Outcome Measure(s)

We examined absolute and variable repositioning errors at increasing shoulder-elevation levels with and without KT application.

Results

Data revealed an interaction between tape and position for absolute error (F_2,52 = 4.07, P = .02); simple effects revealed an increase in error, with KT demonstrating a 2.65° increase in error at 90° of elevation compared with no tape (t₂₆ = 2.65, P = .01). The effect size was medium (ω² = .135). Variable error showed no interaction of tape and position (F_2,52 = .709, P = .50). Further analysis of simple effects was not needed. However, we still calculated the effect size and observed small effect sizes for tape (ω² = .002), position (ω² = .072), and tape by position (ω² = .027).

Conclusions

At 90° of elevation, shoulder JPS was impaired by the application of KT.Key Words: proprioception, taping, shoulder, neuromuscular, rehabilitation

Key Points

• Short-term Kinesio-Tape application to the shoulder reduced joint position sense acuity at 90° of elevation but did not affect JPS at 50° or 110°.
• Kinesio Tape may negatively affect shoulder joint position sense, especially as the shoulder position approaches 90° of elevation.

Athletes, especially those who participate in overhead activities, place much stress on their shoulder joints during activity, so they are at increased risk for developing shoulder injuries. Given that the shoulder allows for much mobility, stability is sacrificed; therefore, the shoulder is considered one of the most vulnerable joints in the body.¹ Numerous factors within the shoulder complex contribute to this lack of stability, including limited glenohumeral bony congruity, limited ligamentous support, and joint capsular laxity. However, stability is still needed to perform precise tasks for activities of daily living or sporting events.² Factors that provide stability to the joint include support of surrounding muscles, the intra-articular pressure of the joint, and the integration of the central nervous system with peripheral mechanoreceptors, a sensory system termed proprioception.³Proprioception is a specialized sensory capability that includes a person''s sense of movement, joint position, and tension.⁴ Joint position sense (JPS) consists of both static and dynamic abilities to detect the position of the joint in space.⁵ Researchers⁶ have suggested that increased muscle activation leads to increased afferent feedback from muscle spindles, resulting in enhanced JPS. The JPS is enabled via sensory feedback from peripheral receptors in sites such as skin, muscles, ligaments, and tendons that the central nervous system processes, and JPS is a key factor for controlling joint movement.⁴Investigators⁷ have observed that shoulder JPS improves as the shoulder-elevation angle approaches 90°. These results may indicate that as the elevation angle increases, the amount of gravitational torque increases, which increases muscle activation. Suprak et al⁷ hypothesized that this increase in muscle activation and the increase in activity from the musculotendinous mechanoreceptors contributed to improved JPS. Suprak et al⁸ supported these results, demonstrating that as resistance increased (via wrist weights) at a given shoulder position, shoulder repositioning error decreased. However, other authors⁵ have suggested that this effect of elevation on shoulder JPS may also be related to intrinsic factors of joint position, such as muscle-spindle and cutaneous-receptor activation.Researchers⁹ believe the application of tape may improve proprioceptive abilities by increasing stimulation of cutaneous mechanoreceptors within the skin, which increases pressure on underlying muscles and, therefore, affects the joint''s proprioception. Robbins et al¹⁰ reported that the application of ankle tape enhanced JPS when a person was on a surface with a slope greater than 10°. Traditional athletic tape can constrict joint range of motion (ROM) but can be a beneficial preventive measure; however, the integrity of the tape is not maintained for extended periods because of such extraneous factors as sweat, lotion, dirt, and hair. Therefore, the development of more specialized tapes that have longer-lasting effects and limit impairments has advanced in recent years. Effective tape application can last up to 1 to 2 days, and some of these specialty tapes can resist extraneous factors.Kinesio Tape (KT; Kinesio Precut, Albuquerque, NM) is a specialized elastic tape that mimics the elasticity of skeletal muscle as it stretches up to 140% of its original length, allowing for no ROM restrictions.^2,11 According to KT creator Kenzo Kase, it can strengthen an already weakened muscle by correcting the muscle''s function, improving circulation of blood and lymph, decreasing pain, repositioning subluxed joints, and improving joint position and kinesthetic awareness.¹² These effects allow the fascia and muscle to return to normal function by relieving the buildup of abnormal muscle tension and can improve joint function by increasing sensory mechanisms.^11,13The constant shear force produced by KT application against the skin leads to increased stimulation of the cutaneous mechanoreceptors.¹⁴ Murray¹⁴ observed an increase in electromyographic measurements after the application of KT to the thigh. He hypothesized that this increased mechanoreceptor activity would result in increased JPS acuity. His research also supported the claim that KT application to the thigh can improve active ROM of a joint compared with no tape.¹⁴ Murray¹⁴ asserted that KT can positively affect proprioception. However, other investigators¹¹ have demonstrated no effect of KT application on the ability to actively replicate a passive ankle position. This discrepancy in observations warrants further investigation given the popularity of KT use in athletics and rehabilitation. No one has examined how KT affects shoulder JPS. Therefore, the purpose of our study was to assess the effects of KT application on shoulder JPS at increasing shoulder elevations in athletes. We hypothesized that the application of KT (1) would result in enhanced shoulder JPS at all elevation angles tested and (2) would not alter the effect of increased JPS acuity with elevation.     

The McConnell Sign is Seen in Patients With Acute Chest Syndrome

Bedside ultrasound is often used as a part of the evaluation of patients who are critically ill. The McConnell sign is an important echocardiographic finding in some critically ill patients with pulmonary embolism and an acute right ventricular infarct. We present 3 critically ill patients with confirmed acute chest syndrome who showed the McConnell sign on echocardiography. In patients with sickle cell disease presenting with chest pain and shortness of breath, the presence of the McConnell sign does not narrow the differential diagnosis between pulmonary embolism, an acute right ventricular infarct, and acute chest syndrome.