Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Topical niacinamide and N-acetyl glucosamine (NAG) each individually inhibit epidermal pigmentation in cell culture. In small clinical studies, niacinamide-containing and NAG-containing formulations reduced the appearance of hyperpigmentation. OBJECTIVES: To assess the effect of a combination of niacinamide and NAG in a topical moisturizing formulation on irregular facial pigmentation, including specific detection of changes in colour features associated with melanin. METHODS: This was a 10-week, double-blind, vehicle-controlled, full-face, parallel-group clinical study conducted in women aged 40-60 years. After a 2-week washout period, subjects used a daily regimen of either a morning sun protection factor (SPF) 15 sunscreen moisturizing lotion and evening moisturizing cream each containing 4% niacinamide + 2% NAG (test formulation; n = 101) or the SPF 15 lotion and cream vehicles (vehicle control; n = 101). Product-induced changes in apparent pigmentation were assessed by capturing digital photographic images of the women after 0, 4, 6 and 8 weeks of product use and evaluating the images by algorithm-based computer image analysis for coloured spot area fraction, by expert visual grading, and by chromophore-specific image analysis based on noncontact SIAscopy for melanin spot area fraction and melanin chromophore evenness. RESULTS: By all four measures, the niacinamide + NAG formulation regimen was significantly (P < 0.05) more effective than the vehicle control formulation regimen in reducing the detectable area of facial spots and the appearance of pigmentation. CONCLUSIONS: A formulation containing the combination of niacinamide + NAG reduced the appearance of irregular pigmentation including hypermelaninization, providing an effect beyond that achieved with SPF 15 sunscreen.

ETS1 and ETS2 in p53 regulation: spatial separation of ETS binding sites (EBS) modulate protein: DNA interaction.

p53 is an extensively studied tumor suppressor gene implicated in the genesis of a large number of varied tumors. However, the pathways of regulation for the wild-type p53 gene and its product are as yet unknown. In situ hybridization analyses of ETS1 and ETS2 expression during mouse embryogenesis, have shown a pattern similar to that of p53 gene expression. Significantly, we have identified several ETS-binding sites (EBS) in the promoter regions of the human and mouse p53 genes. In the human promoter two of these EBS are present in the form of a palindrome, with the two EBS cores being separated by four nucleotides. This report shows that the EBS palindrome of the human p53 promoter has a high affinity for ETS1 and ETS2 and that such binding interaction intracellularly is able to activate the transcription of a CAT reporter gene by 5-10-fold using COS cells. To investigate whether the spacing between the two EBS cores influences the DNA binding activity, we synthesized oligonucleotides with increasing distances (4,12,16, and 20 bases respectively) between the two EBS cores of the palindrome. We observed an inverse correlation between an increasing distance in the two EBS cores of the palindrome and the ETS1 and ETS2 DNA binding activity respectively. Interestingly, optimal DNA binding activity was observed when the distance between the two EBS cores was four bases, identical to that which occurs in the natural promoter. Furthermore we show that the p53 mRNA is expressed at higher levels in NIH3T3 cells overexpressing ETS2 gene product, suggesting that the ETS2 transcription factor is a likely candidate for regulating the expression of p53 in vivo.

Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.

The palmitoyl pentapeptide palmitoyl-lysine-threonine-threonine-lysine-serine (pal-KTTKS) is a synthetic material that was designed as a topical agent to stimulate collagen production and thus provide a skin anti-wrinkle benefit. To determine if pal-KTTKS is effective, the clinical study reported here was conducted. Caucasian female subjects (n = 93, aged 35-55) participated in a 12-week, double-blind, placebo-controlled, split-face, left-right randomized clinical study assessing two topical products: moisturizer control product vs. the same moisturizer product containing 3 ppm pal-KTTKS. Pal-KTTKS was well tolerated by the skin and provided significant improvement vs. placebo control for reduction in wrinkles/fine lines by both quantitative technical and expert grader image analysis. In self-assessments, subjects also reported significant fine line/wrinkle improvements and noted directional effects for other facial improvement parameters.

Basic concepts in family therapy: a differential comparison with individual treatment.

The author presents basic differences between the approaches of family therapy and of the individual therapies on three dimensions: personality development, symptom formation, and the approach to producing therapeutic change. Family therapy bases its view of these factors in psychotherapy on the idea that they are determined by the family's functioning as an interderdependent transactional unit; the individual therapies base their views of these factors on the idea that they are determined by the dynamic intrapsychic functioning of the individual alone.

Laryngeal electromyographic findings in Charcot-Marie-Tooth disease type II.

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy that exhibits progressive muscular atrophy in the limbs, beginning with the lower extremities. It is now understood to be a heterogeneous group of disorders that can be differentiated both clinically and genetically. In Charcot-Marie-Tooth disease type II C, axonal neuropathy, diaphragm weakness, and vocal cord paralysis are described within kindreds. We used laryngeal electromyography to study a patient with this disorder. This technique has potential in the diagnosis of Charcot-Marie-Tooth disease type II.

Quantitative measurement of human physiological age by profiling of body fluids and pattern recognition.

Quantitative correlations with human age are demonstrated for 60 substances from a group of 200 substances measured in the urine of 235 men. Simplified pattern recognition calculations are used to combine these correlations into patterns of human age and to demonstrate their utility for the quantitative measurement of human physiological age and aging rate. The empirical use of these techniques for the extension of human life-span and diminution of human suffering from degenerative diseases is discussed. Current experimental limitations of this method are demonstrated and evaluated. The application of these techniques can form the basis for a significant advance in the quality of human life.

Somatosensory potentials, CSF creatine kinase BB activity, and awakening after cardiac arrest.

OBJECTIVE: To examine the utility of somatosensory evoked potential (SEP) peaks and CSF creatine kinase BB isoenzyme activity (CKBB) in predicting nonawakening from coma due to cardiac arrest. BACKGROUND: Accurate predictors of neurologic outcome in patients comatose after cardiac arrest are needed to improve medical decision making. METHODS: A total of 72 comatose patients had bilateral median SEPs, and of these, 52 had CSF and CKBB. Awakening was defined as following commands or having comprehensible speech. Both short (N1) and long (N3) latency SEP peaks were analyzed. Nonparametric analyses were used. RESULTS: For patients who had both tests, CKBB > or = 205 U/L predicted nonawakening with a sensitivity of 49% and a specificity of 100%. Bilateral absence of the N1 peak predicted nonawakening with a sensitivity of 53% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent SEP N1 peaks, or both predicted nonawakening with a sensitivity of 69% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent N1 peaks, bilateral N3 > or = 176 msec or absent, or some combination predicted nonawakening with a sensitivity of 78% and a specificity of 100%. CONCLUSION: The combination of an absent N1 peak and elevated CKBB performs better than either alone in predicting nonawakening after cardiac arrest. Prolonged or absent N3 latency may increase sensitivity. These results should be interpreted with caution given the small number of patients and the possibility of a self-fulfilling prophecy.

Incidence and natural history of phrenic neuropathy occurring during open heart surgery.

OBJECTIVE: To study the incidence of phrenic neuropathy following coronary artery bypass grafting and determine long-term outcome. DESIGN: Prospective observational. SETTING: Surgical ICU in a university hospital, out-patient follow-up. PATIENTS: Ninety-two consecutive patients undergoing open heart surgery. INTERVENTIONS: None. MEASUREMENTS: Chest radiographs (CXR) 48 to 72 h post-operatively, ultrasonography of diaphragm, phrenic nerve conduction studies, diaphragmatic electromyogram, each repeated every 1 to 3 months until normal. MAIN RESULTS: Seventy-eight of 92 (78 percent) patients had abnormal radiographs, 42 of 78 (54 percent) with abnormal CXRs had abnormal diaphragm motion, 24 of 42 (57 percent) with abnormal motion had phrenic neuropathy. Patients with normal diaphragm motion improved faster than those without; patients with normal nerve conduction (and abnormal motion) improved faster than those with abnormal nerve conduction. CONCLUSIONS: Phrenic neuropathy is relatively common if sensitive tests are utilized for diagnosis. Nerve conduction studies can predict duration of morbidity. Most patients have low morbidity and recover fully. Abnormal diaphragm motion alone is not diagnostic of phrenic nerve injury.

Height is an independent risk factor for neuropathy in diabetic men.

Height may increase the risk of diabetic polyneuropathy, but previous studies are inconclusive. Our purposes were to further examine the hypothesis that height (HT) is an independent risk factor for diabetic polyneuropathy and to determine which electrophysiologic measures are influenced by HT in diabetic subjects. We studied 170 Japanese American men (ages 43-73 years, mean 61) including: 69 diabetic men (mean HT 166 cm), 54 normal men (mean HT 167 cm), and 47 men with impaired glucose tolerance (IGT) (mean HT 164 cm), measuring 28 nerve conduction study (NCS) parameters. We used data from normal men in developing regression models to adjust NCS parameters for HT, age, and temperature. Factor analysis was employed to reduce the 28 NCS parameters to five physiologically meaningful factors, one of which, a factor representing median and peroneal sensory amplitudes, was significantly correlated with HT (r = -0.38, P = 0.0011) in diabetic men; taller subjects having smaller sensory nerve amplitudes. No significant correlation was found between this factor and body mass index. This factor had no correlation with HT in normal or IGT men. Our data do not confirm previous reports of associations between HT and slowed motor conduction velocities in diabetic subjects. This study does, however, support the hypothesis that HT is an independent risk factor for sensory polyneuropathy in diabetic subjects.

Diabetes and diabetes risk factors in second- and third-generation Japanese Americans in Seattle, Washington.

In Seattle, Washington, the prevalence of diabetes was 20% in second-generation (Nisei) Japanese-American men and 16% in Nisei women 45-74 years old, while the prevalence of impaired glucose tolerance (IGT) was 36% in Nisei men and 40% in Nisei women. Hyperglycemia was less and duration of diabetes shorter in women. Related to diabetes and IGT in Nisei were higher fasting plasma insulin levels and central (visceral) adiposity. Prevalence of diabetes was low among the younger (34-53 years old) third-generation (Sansei) men and women. Among self-reported non-diabetic Sansei, however, prevalence of IGT was 19% in men and 29% in women, and IGT was associated with both increased fasting plasma insulin levels and more visceral fat, suggesting that many Sansei are at risk of future diabetes. An important lifestyle factor in the development of NIDD in Japanese Americans appeared to be dietary saturated (animal) fat. Another factor may be physical inactivity. In Japanese-American women, menopause also appeared to be an important risk factor. These risk factors may be related to fostering the accumulation of visceral fat and the development of insulin resistance. Five-year follow-up examinations performed in non-diabetic Nisei men and women have yielded additional information concerning the prognosis of IGT. Of those women who were IGT at baseline, 34% were diabetic at follow-up while 17% returned to normal. In men who had been IGT at baseline, 18% were diabetic at follow-up while 36% returned to normal. Over the 5-yr follow-up interval, proportionally more women progressed from normal to IGT (54%) then went from IGT to normal (17%). For men, roughly equal proportions went from normal to IGT (37%) as from IGT to normal (36%). It would therefore appear that greater proportions of Nisei women are progressing to IGT and to NIDD than are Nisei men. This observation may be related to the increased risk of developing central obesity and insulin resistance following menopause. Prevalence of cardiovascular disease (hypertension, peripheral vascular disease, and/or coronary heart disease) was increased in Japanese Americans with IGT and NIDD. Neuropathy and retinopathy were associated only with NIDD.

Idiopathic bilateral vocal fold weakness.

OBJECTIVE: To describe an unrecognized clinical entity, idiopathic bilateral vocal fold weakness, and propose recommendations regarding the diagnosis and management of these cases. STUDY DESIGN: Retrospective, nonrandomized case study. METHODS: All cases of bilateral vocal fold weakness evaluated at the University of Washington Voice Disorders Clinic between 1991 to 1998 were reviewed. RESULTS: Four patients with bilateral laryngeal weakness were determined to have idiopathic bilateral vocal fold paresis following exhaustive workups, including videostroboscopy, bilateral laryngeal electromyography (EMG), neurological consultation, and other pertinent studies. CONCLUSIONS: Performing bilateral laryngeal EMG is an essential aspect of the workup of any laryngeal weakness case, particularly if the etiology is unknown on presentation. Idiopathic bilateral vocal fold weakness is an underrecognized but real clinical diagnosis that will become more familiar with the increasing utilization of laryngeal EMG in clinical situations.

New laryngeal muscle weakness in post-polio syndrome.

The authors describe the clinical presentations of post-polio laryngeal muscle weakness in three patients with prior polio infection who presented with new complaints including slowly progressive dyspnea, dysphagia, and/or hoarseness. Evaluations by laryngeal videostroboscopy and electromyography revealed vocal cord abductor and/or adductor weakness, recurrent posterior glottic web in one case, and, in the two patients who agreed to electromyography, evidence of prior denervation and reinnervation in laryngeal muscles. Treatment was directed at attempting to maintain an airway and optimize vocal quality. One patient benefitted from tracheostomy, one benefitted from vocal cord medialization, and one benefitted from resection of interarytenoid scarring. The authors conclude that diagnosis of laryngeal post-polio syndrome is facilitated by laryngeal electromyography. Interventions directed at maintaining an appropriate airway and optimizing vocal quality may be helpful.

Combined effects of compression and hypotension on nerve root function. A clinical case.

Previous animal experiments suggest that mild compression may increase susceptibility of nerve roots to the effects of hypotension. The authors report the case of a patient with an unstable L2 burst fracture whose motor skills and senses were intact. During fracture reduction and spinal distraction, sensory-evoked potentials were recorded from the epidural space after right and left femoral and tibial nerve stimulation. Induced hypotension was used during the surgery. All responses were normal at the outset of the surgery. With hypotension, a marked drop in the amplitude of the right femoral evoked potential amplitude occurred; left femoral and both tibial responses remained unchanged. Evoked potential changes were reversible with reversal of hypotension. Postoperatively, the patient was neurologically intact. Further analysis revealed a significant correlation between the right femoral evoked potential amplitude and systolic blood pressure (r = 0.63, P < 0.005), whereas amplitudes of the other responses were not significantly correlated with systolic blood pressure. This report provides clinical evidence to support the hypothesis that hypotension and local compression exert additive adverse effects on nerve root function.

The efficacy of femoral nerve intraoperative somatosensory evoked potentials during surgical treatment of thoracolumbar fractures.

Somatosensory evoked potential (SEP) monitoring of thoracolumbar procedures typically includes posterior tibial and peroneal nerve recordings. The addition of femoral nerve SEP monitoring, however, should better predict the evolution of postoperative neurologic deficits affecting the midlumbar roots. To assess the value of intraoperative femoral SEPs, 26 cases of traumatic injury to the thoracolumbar spine between T12 and L4 were prospectively assessed. Twenty-four had clear femoral nerve responses bilaterally recorded from an epidural electrode. Five had significant intraoperative SEP changes: one had isolated femoral nerve changes, two had only peroneal or tibial nerve changes, and two had concomitant changes in both femoral and peroneal or tibial nerves. Loss of the femoral nerve response in one patient was correlated with marked postoperative knee extensor weakness, in spite of immediate action taken by the surgeon. The authors conclude that femoral nerve SEPs provide an effective tool to monitor the midlumbar roots intraoperatively.

Laryngeal electromyography for the diagnosis and management of swallowing disorders.

Laryngeal electromyography has proved useful for the evaluation of neurologic disorders of the larynx. The techniques for this procedure are also well suited to investigate disorders of the pharyngeal phase of swallowing. The responses from the thyroarytenoid muscles, the cricothyroid muscles, and the cricopharyngeus muscle can offer information to aid in the diagnosis, prognosis, and in some cases, treatment of dysphagia. A general review of electromyographic responses with sample tracings from the larynx are included in this article.

Role of neurophysiologic evaluation in diagnosis.

The electrodiagnostic evaluation assesses the integrity of the lower-motor-neuron unit (i.e., peripheral nerves, neuromuscular junction, and muscle). Sensory- and motor-nerve conduction studies measure compound action potentials from nerve or muscle and are useful for assessing possible axon loss and/or demyelination. Needle electromyography measures electrical activity directly from muscle and provides information about the integrity of the motor unit; it can be used to detect loss of axons (denervation) as well as reinnervation. The electrodiagnostic examination is a useful tool for first detecting abnormalities and then distinguishing problems that affect the peripheral nervous system. In evaluating the patient with extremity trauma, it can differentiate neurapraxia from axonal transection and can be helpful in following the clinical course. In patients with complex physical findings, it is a useful adjunct that can help discriminate motor neuron disease from polyneuropathy or myeloradiculopathy due to spondylosis.

Correlation between stroboscopy and electromyography in laryngeal paralysis.

Twenty patients with vocal fold motion impairment were reviewed to correlate the findings of electromyography (EMG) and stroboscopy. The causes of motion impairment were idiopathic, previous surgery with recurrent laryngeal nerve injury, neck and skull base trauma, and neoplasm. The EMG studies were analyzed to assess the status of innervation of the immobile vocal fold. The presence or absence of the mucosal wave prior to therapeutic intervention was determined with stroboscopic examination. Eight of 10 patients with EMG evidence of reinnervation or partial denervation were found to have mucosal waves, and 3 of 10 patients with EMG evidence of denervation were found to have mucosal waves. Six patients developed mucosal waves after surgical medialization, despite evidence of denervation by EMG criteria. These findings support the premise that tension and subglottic pressure, rather than status of innervation, determine the presence of the mucosal wave.

Somatosensory evoked potential monitoring during closed humeral nailing: a preliminary report.

OBJECTIVES: To assess the role of intraoperative somatosensory evoked potential (SSEP) monitoring of the radial and median nerves in preventing iatrogenic nerve injury during closed, locked intramedullary (IM) nailing of the humerus. DESIGN: Prospective clinical study. SETTING: Pacific Northwest Level One trauma center and Southern California military medical center. PATIENTS: Thirteen patients with indications for surgical stabilization of fractures of the humeral diaphysis and either unknown neurologic status of the affected limb or anticipated difficult reduction maneuvers due to fracture complexity or displacement. INTERVENTION: Closed, antegrade or retrograde locked IM nailing of the humerus was attempted while intraoperative monitoring of the radial and median nerves with SSEP was performed. MAIN OUTCOME MEASUREMENTS: Intraoperative radial and median nerve SSEP changes during closed fracture manipulation, guide rod insertion, reaming, and humeral nail placement. RESULTS: Baseline recordings were obtained in twelve of thirteen patients for both the radial and median nerves. An absence of radial nerve signal in one patient with a closed head injury prompted an open procedure, revealing entrapment of the radial nerve in the fracture. Intraoperative SSEP changes were observed in two of the twelve remaining patients during fracture manipulation and distal interlocking. The signal amplitude returned after discontinuation of manipulation and traction, and alteration of the interlocking maneuver. No neurologic deficits were noted in these two patients. CONCLUSIONS: Intraoperative radial nerve SSEP monitoring appears to reliably reflect the status of the radial nerve in those patients with a humerus fracture. In three of eleven patients, intraoperative signal changes prompted a change in surgical plan. In no patient did there appear to be evidence of iatrogenic nerve injury.

Considerations in reference values for nerve conduction studies.

Despite the universal application of reference values, understanding their production and underlying limitations is often overlooked. Without a deeper consideration for this issue, opportunities for treatment may be missed or misdiagnosis may occur. This article reviews relevant biostatistical issues in the generation of reference intervals and subsequent errors that may occur. Further discussion includes recommendations on how to correct statistical errors, as well as more recent methods for distinguishing between "healthy" and "diseased."

Neurophysiological function in farm workers exposed to organophosphate pesticides.

To investigate neurophysiological effects of low-level exposure to foliar organophosphate residues during one season among agricultural workers, the authors performed a cross-sectional study of 67 Hispanic farm workers and 68 age-, gender-, ethnicity-, and education-matched reference subjects. The neurophysiological examination included sensory and motor nerve conduction and neuromuscular junction testing. Erythrocyte cholinesterase activity was measured at the time of examination. No statistically significant neurophysiological differences between the exposed and reference groups were observed. Farm workers and reference subjects had similar sensory nerve latency and amplitude (sural), motor nerve conduction velocity (ulnar), and neuromuscular junction function (ulnar). No relationship between duration of exposure during the season and electrophysiological measures of nerve function was found. Exposure of farm workers to the low levels of organophosphate pesticides during one season experienced by farm workers in this study was not associated with impaired peripheral neurophysiological function.