Prognosis and Management of Congenital Hair Shaft Disorders with Fragility—Part I

Hair shaft disorders are characterized by congenital or acquired abnormalities of the hair shaft. The objective was to review the literature regarding the prognosis and treatment options of hair shaft disorders. We used keywords in the search engines PubMed and Medline to identify all publications in the English language related to the prognosis and management of hair shaft disorders. Data were extracted from 96 articles that met search criteria. Findings were limited to case reports and small case series, as no studies were found. Disorders that improve in childhood include pili torti, trichorrhexis invaginata, wooly hair, and pili trianguli et canaliculi. Others, such as trichorrhexis nodosa, monilethrix, pili annulati, and pili bifurcati improve with minoxidil. Oral retinoids have improved hair abnormalities in trichorrhexis invaginata and monilethrix. There is no specific treatment for congenital hair shaft abnormalities. Gentle hair care is the mainstay of care for hair shaft disorders associated with fragility. Practices for gentle care include no brushing, backcombing, chemical products, tight braids, heat exposure, or mechanical grooming. Any inherited or congenital disorder requires genetic counseling as part of management.     

Prognosis and Management of Congenital Hair Shaft Disorders without Fragility—Part II

Hair shaft disorders are characterized by congenital or acquired abnormalities of the hair shaft. The objective of this study was to review the literature regarding the prognosis and treatment options for hair shaft disorders. We used keywords in the search engines PubMed and Medline to identify all publications in English related to the prognosis and management of hair shaft disorders. Data were extracted from 96 articles that met search criteria. Findings were limited to case reports and small case series, as no studies were found. Disorders that improve in childhood include pili torti, trichorrhexis invaginata, woolly hair, and pili trianguli et canaliculi. Others, such as trichorrhexis nodosa, monilethrix, pili annulati, and pili bifurcati, improve with minoxidil. Oral retinoids have been found to improve hair abnormalities in trichorrhexis invaginata and monilethrix. There is no specific treatment for congenital hair shaft abnormalities. Gentle hair care is the mainstay of care for hair shaft disorders associated with fragility. Practices for gentle care include no brushing, backcombing, chemical products, tight braids, heat exposure, or mechanical grooming. Furthermore, any inherited or congenital disorder requires genetic counseling as part of management.     

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Shear Wave Elastography of Peripheral Muscle Weakness in Patients with Chronic Congestive Heart Failure

Forty-five study participants (28 chronic heart failure [CHF] patients and 17 control participants) were prospectively enrolled in this study to investigate the clinical potential of ultrasound shear wave elastography (SWE) in identifying peripheral muscle weaknesses in chronic heart failure patients. Muscle stiffness in the gastrocnemius muscle during extension (stretch) and the lower arm flexor muscles during flexion was assessed via shear wave elastography, measuring the shear modulus (kPa) for the resting and contractile states in a range of 0–300 kPa. Resting kPa revealed no significant difference between CHF and CP, but exercise kPa for extension and flexion was significantly lower in CHF than CP. The area under the receiver operating characteristic curve of the denominator kPa-Exercise stretch was 0.916, associated with a sensitivity of 89%, a specificity of 71% and a corresponding cutoff value of 81.1 kPa. Shear wave elastography is thus a reproducible and sensitive ultrasound method for evaluating peripheral muscle deficits in patients with CHF.     

A Monte Carlo approach for improving transient dopamine release detection sensitivity

Current methods using a single PET scan to detect voxel-level transient dopamine release—using F-test (significance) and cluster size thresholding—have limited detection sensitivity for clusters of release small in size and/or having low release levels. Specifically, simulations show that voxels with release near the peripheries of such clusters are often rejected—becoming false negatives and ultimately distorting the F-distribution of rejected voxels. We suggest a Monte Carlo method that incorporates these two observations into a cost function, allowing erroneously rejected voxels to be accepted under specified criteria. In simulations, the proposed method improves detection sensitivity by up to 50% while preserving the cluster size threshold, or up to 180% when optimizing for sensitivity. A further parametric-based voxelwise thresholding is then suggested to better estimate the release dynamics in detected clusters. We apply the Monte Carlo method to a pilot scan from a human gambling study, where additional parametrically unique clusters are detected as compared to the current best methods—results consistent with our simulations.     

Evaluating the validity of model for end‐stage liver disease exception points for hepatocellular carcinoma patients with multiple nodules <2 cm

Liver transplant allocation policy does not give model for end‐stage liver disease (MELD) exception points for patients with a single hepatocellular carcinoma (HCC) <2 cm in size, but does give points to patients with multiple small nodules. Because standard‐of‐care imaging for HCC struggles to differentiate HCC from other nodules, it is possible that a subset of patients receiving liver transplant for multiple nodules <2 cm in size does not have HCC. We evaluate risk of post‐transplant HCC recurrence and wait‐list dropout for patients with multiple small nodules using competing risks regression based on the Fine and Gray model. We identified 5002 adult HCC patients in the OPTN/UNOS dataset diagnosed and transplanted between January 2006 and September 2010. Compared to patients with >1 tumor <2 cm, risk of developing recurrence was significantly higher in patients with one or more tumors with only one tumor ≥2 cm (SHR 1.63, p = 0.009), as well as in patients with 2–3 tumors ≥2 cm (SHR 1.84, p = 0.02). Dropout risk was not significantly different among size categories. HCC recurrence risk was significantly lower in patients with multiple nodules <2 cm in size than in those with larger tumors, supporting the possibility that some patients received unnecessary transplants. The priority given to these patients must be re‐examined.     

The role of oxygen as a regulator of stem cell fate during fracture repair in TSP2‐null mice

It is often difficult to decouple the relative importance of different factors in regulating MSC differentiation. Genetically modified mice provide model systems whereby some variables can be manipulated while others are kept constant. Fracture repair in thrombospondin‐2 (TSP2)‐null mice is characterized by reduced endochondral ossification and enhanced intramembranous bone formation. The proposed mechanism for this shift in MSC fate is that increased vascular density and hence oxygen availability in TSP2‐null mice regulates differentiation. However, TSP2 is multifunctional and regulates other aspects of the regenerative cascade, such as MSC proliferation. The objective of this study is to use a previously developed computational model of tissue differentiation, in which substrate stiffness and oxygen tension regulate stem cell differentiation, to simulate potential mechanisms which may drive alterations in MSC fate in TSP2‐null mice. Four models (increased cell proliferation, increased numbers of MSCs in the marrow decreased cellular oxygen consumption, and an initially stiffer callus) were not predictive of experimental observations in TSP2‐null mice. In contrast, increasing the rate of angiogenic progression led to a prediction of greater intramembranous ossification, diminished endochondral ossification, and a reduced region of hypoxia in the fracture callus similar to that quantified experimentally by the immunohistochemical detection of pimonidazole adducts that develop with hypoxia. This study therefore provides further support for the hypothesis that oxygen availability during early fracture healing is a key regulator of MSC bipotential differentiation, and furthermore, it highlights the advantages of integrating computational models with genetically modified mouse studies for further elucidating mechanisms regulating stem cell fate. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1585–1596, 2013.