A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter

Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share common gain-of-function mutations. Mutation prevalence varies greatly and is inversely related to iodine intake of the population. We report a Greek patient presenting with subclinical hyperthyroidism due to a fast-growing autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA sequencing showed that the hot nodule harbored a somatic heterozygous activating TSHR mutation: substitution of glutamine for leucine in the third transmembrane helix. This mutation (L512Q) was recently described in two solitary toxic adenomas. This report expands the spectrum of mutations shared by dissimilar hot nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The identification of the L512Q substitution demonstrates that gain-of-function TSHR mutations are encountered in Greece, although iodine deficiency has been significantly corrected over the last three decades.     

Diagnostic steps in the evaluation of patients with erectile dysfunction

PURPOSE: The necessity for a thorough diagnostic evaluation for erectile dysfunction has been questioned after the availability of effective oral therapies. We determined the impact of the different diagnostic steps on the management strategy for erectile dysfunction. MATERIALS AND METHODS: The study included all patients who presented at an andrology outpatient clinic during a 4-year period. Baseline evaluation included medical and sexual history, blood tests, physical examination and intracavernous injection test. Patients with normal initial screening were evaluated with specific diagnostic procedures. The results were analyzed to identify the diagnostic potential of each screening step separately. RESULTS: Overall 1,644 patients presented at the clinic during the study period, of whom 368 (22.4%) were excluded from study due to severe psychiatric (5.2%) or cardiovascular (2.7%) disease, or to a history of erectile dysfunction less than 3 months in duration (14.5%). In the remaining 1,276 patients with a mean age plus or minus standard deviation of 56 +/- 14 years, and a mean duration of erectile dysfunction of 4.9 +/- 3.4 years medical history revealed erectile dysfunction associated medical conditions in 57%, blood tests identified previously undiagnosed medical conditions in 6.2%, and physical examination and the intracavernous injection test were diagnostic in 13.9% and 2.6%, respectively. Initial screening was negative in 259 cases (20.3%), in which specific diagnostic procedures identified an underlying vascular pathology in 165 (12.9%) and unfavorable penile geometry in 16 (1.3%). The remaining 78 men (6.1%) had no evidence of organic disease. CONCLUSIONS: Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction associated risk factors in 80% of patients. Such screening may diagnose reversible causes of erectile dysfunction and also unmask medical conditions that manifest with erectile dysfunction as the first symptom. Specific diagnostic procedures may be limited in patients with primary erectile dysfunction or those without risk factors. Such clinical data support previously published guidelines for erectile dysfunction management.     

Management strategy for arterial priapism: therapeutic dilemmas

PURPOSE: We present 7 cases of arterial high flow priapism and propose management algorithms for the condition. MATERIALS AND METHODS: We studied 2 children and 5 adults with posttraumatic arterial priapism. Blood gas analysis and color Doppler ultrasonography of the corpora cavernosa confirmed the diagnosis in 4 adults, while 1 patient had already undergone cavernous artery ligation in elsewhere. In the children perineal compression resulted in detumescence, a sign that is proposed to be indicative of the diagnosis of arterial priapism (piesis sign) complementing physical examination. Mechanical compressive force was applied to the perineum of 1 boy, while the other received a watchful waiting program. All adults participated in an observation regimen except 1, who decided to undergo immediate embolization of the internal pudendal artery. RESULTS: Perineal compression led to the resolution of priapism in 1 child, while spontaneous resolution was noted in the other. An adult noticed spontaneous penile detumescence 3 to 4 months after trauma, which was attributable to site specific venous leakage and decreased, inflow in the contralateral cavernous artery. The patient underwent venous surgery and is on an intracavernous injection regimen. Successful embolization of the internal pudendal artery was performed immediately in 1 man and in the other 4 months after trauma due to social inconvenience. Adult patient 3 is still on the watchful waiting protocol (42 months), while the one who underwent cavernous artery ligation is receiving treatment for erectile dysfunction. CONCLUSIONS: Absent of long-term damaging effects of arterial priapism on erectile tissue combined with the possibility of spontaneous resolution or progressive concomitant hemodynamic abnormalities associated with blunt perineal trauma are suggestive of the introduction of an observation period in the management algorithm of high flow priapism. Such a period may help avoid unnecessary intervention and determine the impact of priapism on patient personal life. Perineal compression may be also added as part of the physical examination as a sign specifically indicative of arterial priapism.     

Photomechanical delivery of 100-nm microspheres through the stratum corneum: implications for transdermal drug delivery

BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis.     

Lateralised motor control: hemispheric damage and the loss of deftness

OBJECTIVE: To learn if the left compared with the right hemisphere of right handed subjects exerts bilateral compared with contralateral motor control when performing precise and coordinated finger movements. METHODS: The study investigated intertask differences of manual motor asymmetries such as speed, precision, and independent finger movements, in patients with unilateral lesions of the left (LHD) or right hemisphere (RHD) and normal controls (C). RESULTS: Normal subjects showed the greatest right hand preference on a task that required rapid coordinated and precise independent finger movements (coin rotation). Both hemisphere damaged groups revealed contralateral motor deficits, but the magnitudes of asymmetries were found to be significantly different (RHD>C>LHD) with contralateral and ipsilateral deficits for LHD subjects. The greatest ipsilateral deficits for the LHD subjects were on those tasks that require precision (grooved pegboard and coin rotation). CONCLUSIONS: The degree of hemispheric specialisation is, in part, dependent upon the nature of the motor task, with left hemisphere motor control necessary for tasks that require precision and coordinated independent finger movements.     

Contribution of MRI and MR angiography in early diagnosis of brain death

The objective of this study was to investigate whether the findings of MR imaging and MR angiography could accurately and early diagnose brain death in comatose patients. Thirty comatose patients were studied with MRI and MR arteriography. In 20 patients (group A) presenting with a Glasgow coma scale (GCS) 3–6, the final clinical diagnosis was brain death. In ten comatose patients with a GCS 4–6 and no clinical signs of brain death (group B), the clinical follow-up did not reveal brain death in a period of 12 months. The MRI examination consisted of turbo fluid-attenuated inversion recovery and T2 turbo spin-echo pulse sequences. The MR arteriography was performed with a 3D inflow pulse sequence. In 12 patients with brain death and 5 patients with no signs of brain death, a 3D phase contrast MR venography was also applied. Magnetic resonance imaging in all patients showed variable edema with swelling of the cerebral gyri, small ventricular system, and basilar subarachnoid spaces. In group A, MRI in addition showed tonsillar herniation. In group A, MR arteriography revealed no arterial flow in the intracranial circulation, whereas MR venography showed in 9 patients no opacification of the sagittal and straight sinuses or visualization of intracranial veins. In contrast, MR angiography showed intact intracranial vessels in patients of group B. In conclusion, MR imaging and MR angiography may be reliable ancillary tests for use in early diagnosis of brain death and further work is required to validate its utility. Electronic Publication     

The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

Background  

Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants.     

The effects of nebulized salbutamol, external positive end-expiratory pressure, and their combination on respiratory mechanics, hemodynamics, and gas exchange in mechanically ventilated chronic obstructive pulmonary disease patients

We hypothesized that combined salbutamol and external positive end-expiratory pressure (PEEPe) may present additive benefits in chronic obstructive pulmonary disease (COPD) exacerbation. In 10 anesthetized, mechanically ventilated, and bronchodilator-responsive COPD patients exhibiting moderate intrinsic PEEP (PEEPi), we assessed respiratory system (rs) mechanics, hemodynamics, and gas exchange at (a) baseline (zero PEEPe [ZEEPe]), (b) 30 min after 5 mg of nebulized salbutamol administration (ZEEPe-S), (c) 30 min after setting PEEPe at baseline PEEPi level (PEEPe), and (d) 30 min after 5 mg of nebulized salbutamol administration with PEEPe maintained unchanged (PEEPe-S). Return of determined variable values to baseline values was confirmed before PEEPe application. Relative to ZEEPe, (a) at ZEEP-S, PEEPi (4.8 +/- 0.7 versus 7.0 +/- 1.1 cm H(2)O), functional residual capacity change (115.6 +/- 23.1 versus 202.1 +/- 46.0 mL), minimal rs (airway) resistance (9.3 +/- 1.4 versus 11.8 +/- 2.2 cm H(2)O.L(-1).s(-1)), and additional rs resistance (5.2 +/- 1.4 versus 7.2 +/- 1.3 cm H(2)O.L(-1).s(-1)) were reduced (P < 0.01), and hemodynamics were improved; (b) at PEEPe, PEEPi (3.7 +/- 1.3 cm H(2)O) was reduced (P < 0.01), and gas exchange was improved; and (c) at PEEPe-S, PEEPi (2.0 +/- 1.2 cm H(2)O) was minimized, and rs mechanics (static rs elastance included), hemodynamics, and gas exchange were improved. Conclusively, in carefully preselected COPD patients, bronchodilation/PEEPe exhibits additive benefits.