Autologous Cultured Fibroblast Injection for Facial Contour Deformities: A Prospective, Placebo-Controlled, Phase III Clinical Trial

BACKGROUND: Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen. OBJECTIVE: The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects. METHODS: This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection. RESULTS: Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12-month follow-up, live fibroblast-treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported. CONCLUSIONS: Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection.     

Clinical Experience with Light-Emitting Diode (LED) Photomodulation

Background. Light-emitting diode (LED) photomodulation is a novel nonthermal technology used to modulate cellular activity with light.
Objective:. We describe our experience over the last 2 years using 590 nm LED photomodulation within a dermatologic surgery environment.
Methods. Practical use of nonthermal light energy and emerging applications in 3,500 treatments delivered to 900 patients is detailed.
Results. LED photomodulation has been used alone for skin rejuvenation in over 300 patients but has been effective in augmentation of results in 600 patients receiving concomitant nonablative thermal and vascular treatments such as intense pulsed light, pulsed dye laser, KTP and infrared lasers, radiofrequency energy, and ablative lasers.
Conclusion:. LED photomodulation reverses signs of photoaging using a new nonthermal mechanism. The anti-inflammatory component of LED in combination with the cell regulatory component helps improve the outcome of other thermal-based rejuvenation treatments.     

Adverse learning strategy: the Adelaide Diagnostic Learning Inventory and its subscale replicability in a medical student population

The Adelaide Diagnostic Learning Inventory (ADLIMS) is a measure of learning styles and learning pathologies that was designed to investigate the impact of traditional approaches to learning versus problem-based learning and to identify students whose approach to learning tasks predicted poor academic performance. In this study, some important psychometric properties of the ADLIMS were examined, including its factor structure. In this study, factor replicability across samples was argued to provide a more robust and psychologically meaningful factor solution than that which can be obtained using traditional mathematical criteria. The results of the factor analysis did not confirm the presence of the four factor solution earlier reported for the ADLIMS, but did identify three clear factors that had very high replicability. An inspection of the items comprising these three factors showed that factor 1 tapped subjective distress related to poor study habits, lack of motivation to study, and distraction from social activities. Factor 2 tapped distress arising from high achievement expectations that were hampered by superficial or disorganized study habits that did not enable the student to grasp the relationships between concepts and ideas. Factor 3 tapped positive feelings and a sense of satisfaction associated with a problem-based approach to the learning of new study material. Although the internal reliability of the ADLIMS subscales met the requirements of a measure to be used in general research such as in the investigation of correlates among groups of medical students, they did not meet the higher requirements of a measure to be used to identify or predict individuals with pathological learning styles.     

The application of basic science concepts to clinical problem-solving

This study looks at the relationship between anatomical concepts held by medical students and their clinical application, and develops a testable model of how students use basic science concepts for clinical problem-solving. According to the model, the essential prerequisites to solve a clinical problem using basic science information include the appropriate basic science knowledge, the ability to collect and interpret clinical information, with the key concept being the link that must then be made between clinical data and basic science. A detailed analysis of the individual components of the model should help to clarify and resolve some of the debate about the nature and balance of basic science and clinical education. A neurological diagnostic problem was used to test the assumptions of the model in a group of medical students who had minimal clinical experiences. There was no demonstrable relationship between anatomical knowledge as assessed by conventional tests and the diagnosis. There was a powerful relationship between measures of organization of knowledge and diagnosis, suggesting that the organization and development of concepts is the key to correct diagnosis. The findings have significant implications for assessment purposes and suggest that standard methods as generally practised may not measure the appropriate conceptual development and are not congruent with curricular objectives. Through the examination of its different learning outcome measures, the model may also be used to provide a profile of individual students or classes, which should help teachers and students deal with difficulties that may be experienced in learning to link clinical and basic science concepts.     

Who speaks for the children?

• ? It would probably be a truism to say that most professional nurses consider patient/client advocacy to be an essential component of their role—indeed, there is a UKCC Advisory paper (Exercising Accountability, 1989), which categorically states that this is so. ‘The introductory paragraphs of the Code of Professional Conduct, together with several of its clauses, include clearly the expectation that the practitioner will accept a role as an advocate on behalf of his or her patients/clients.’
• ? Some professional nurses, however, consider advocacy to be too altruistic an activity and prefer to leave it to others.

     

Viral Persistence in Neurons Alters Synaptic Plasticity and Cognitive Functions without Destruction of Brain Cells

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.     

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats

Cardiovascular ‘reactivity’ to graded splanchnic nerve stimulations was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/r₁ of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle.     

Neurite outgrowth-regulating properties of GABA and the effect of serum on mouse spinal cord neurons in culture

Time-lapse photography was used to examine the effects of γ-aminobutyric acid (GABA) on the outgrowth and motility of neurites in cultures from mouse spinal cord. GABA at concentrations of 100, 10 and 1 μ m caused significant inhibition of neurite outgrowth and the motility of growth cones was significantly reduced by treatment with 100 and 10 μ m GABA. This effect was mimicked by the GABA_B receptor agonist baclofen, whereas the GABA_A receptor agonist muscimol had no effect. The effect of GABA on outgrowth and motility seems to be dependent on the type of serum employed. The results reported here were obtained only when heat-inactivated serum was used and not when non heat-inactivated serum was added to the culture medium. They suggest that GABA has a role in the regulation of process outgrowth within the embryonic mouse spinal cord.     

Delayed Enhancement of Acetaminophen Hepatotoxicity by General Anesthesia Using Diethyl Ether or Halothane

Delayed Enhancement of Acetaminophen Hepatotoxicity by GeneralAnesthesia Using Diethyl Ether or Halothane. WELLS, P. G., RAMJI,P., AND KU, M. S. W. (1986). Fundam. App. Toxicol 6, 299–306.Acetaminophen (Tylenol) is a widely used analgesic/antipyreticdrug which is enzymatically bioactivated, or toxified, by thecytochromes P-450 to a hepatotoxic reactive intermediary metabolite.Brief general anesthesia with diethyl ether has been shown toinhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation,the latter constituting up to 60% of acetaminophen eliminationvia a nontoxifying pathway. Thus ether potentially could producea temporally differentiated inhibition of bioactivating and"detoxifying" pathways, resulting in an enhancement of acetaminophenhepatotoxicity if the balance favored bioactivation. To evaluatethis possibility, separate groups of male NIH strain mice weretreated with acetaminophen at different times after 5 min ofanesthesia with ether. Ether produced a 40-fold enhancementin acetaminophen hepatotoxicity as determined by plasma glutamic-pyruvictransaminase (GPT) concentrations. This toxicologic enhancementwas observed only if acetaminophen administration was delayed,with a maximal enhancement when acetaminophen was given 6 hrafter ether, and no effect with a delay of 16 hr. Similar studiesin male CD-1 mice were carried out using halothane (Fluothane)as the general anesthetic given either over 5 min or over 1hr. While halothane given over 5 min had no effect, a 1 hr anestheticduration produced a 10-fold increase in acetaminophen hepatotoxicityas determined by peak GPT concentration, with no observed hepatotoxicityin the halothane controls. Toxicologic enhancement occurredonly with delayed administration of acetaminophen; however,the maximal enhancement observed with a 6-hr delay was stillevident with a 12-hr delay. Conversely, inhibition of acetaminophenhepatotoxicity was observed if acetaminophen was given either2 hr or 18 hr after halothane. These observations may have clinicalrelevance, and they indicate potential complications in theinterpretation of results obtained from animals subjected togeneral anesthesia.