Defining characteristics of financially successful orthodontists.

Financially successful personality profiles in most of the business world have been reported to be the choleric (powerful) and the melancholy (perfect) types. In 1996, Hughes proposed that the same relationship possibly exists in the profession of orthodontics. The purpose of this study was to explore whether a dominant personality profile exists for the most financially successful orthodontists. A questionnaire was used to gather information regarding the financial sophistication and the dominant personality profile of each participating orthodontist. One hundred twenty-six of the 300 surveys distributed to orthodontists were returned for a response rate of 42%. For every question, the null hypothesis of independence was tested with the chi-square test. The null hypothesis of independence was rejected for a P value of less than.05. The results revealed that no correlation exists between the financial sophistication of orthodontists and their personality profiles. However, over two thirds of the orthodontists had the choleric (powerful) and the melancholy (perfect) as dominant personality types. Interestingly, the questionnaire shed much light on factors that do contribute to financial success in orthodontics. Although statistical differences are lacking in these data, certain traits about successful practitioners could be identified. These orthodontists (1) allow their practices to grow if it will increase the net income, (2) view control of overhead as a key principle, (3) emphasize the competence of staff in determining the success of practice, and (4) believe in marketing. Implementation of these simple and common sense principles in some orthodontic practices might affect the business significantly.

Reduced hyperalgesia in nerve-injured WLD mice: relationship to nerve fiber phagocytosis, axonal degeneration, and regeneration in normal mice.

The pathogenesis of neuropathic pain states is influenced by inflammatory factors associated with nerve injuries and may be mediated in part by the macrophage-dependent process of Wallerian degeneration. Macrophages play a dominant role in the Wallerian (axonal) degeneration that characterizes the painful chronic constriction injury model of neuropathy by liberating proinflammatory cytokines at the site of nerve injury. These cytokines directly affect the structural integrity of neural systems and have been implicated in the development of hyperalgesic states. We hypothesized that interference with the pathologic process of Wallerian degeneration would alter the development of the neuropathic pain state. To test this hypothesis, we studied the development of thermal hyperalgesia in the chronic constriction injury model of neuropathy using normal mice and mice of the WLD strain in which recruitment of macrophages to the site of nerve injury and Wallerian degeneration are delayed. We compared the onset and magnitude of the hyperalgesia with quantitative measures of nerve injury including the phagocytic cellular activity associated with Wallerian degeneration. In C57BL/6J (6J) mice, hyperalgesia peaked 3-10 days after placement of the ligatures, qualitatively matching the response previously reported for rats. In C57BL/WLD (WLD) mice, there was reduced hyperalgesia temporally associated with reduced numbers of phagocytic cells in the injured nerve. In injured WLD nerves there was a reduced rate of axonal degeneration compared to similarly injured 6J nerves. Regeneration was correspondingly delayed in the WLD animals. The results suggest that the process of Wallerian degeneration is a key factor in the pathogenesis of hyperalgesia. Continued development of mouse models of neuropathic pain will be important in exploring the molecular basis of neuropathic pain. Interference with the cellular mediators of Wallerian degeneration may be a useful therapeutic strategy that might modulate the onset and magnitude of hyperalgesia following nerve injury.

Axonal viability and the persistence of thermal hyperalgesia after partial freeze lesions of nerve.

Partial freeze injuries of rat sciatic nerve have been used to investigate the relationship between the amount of tissue injured and the magnitude and duration of the resulting thermal hyperalgesia. Complete freeze injury of peripheral nerve produces temporary anesthesia to peripheral stimuli and is a useful neurolytic technique. The present study examined the hypothesis that incomplete nerve lesions, in which some fibers survive while others undergo Wallerian (axonal) degeneration, lead to development of thermal hyperalgesia. In this study, performed on rats, one sciatic nerve was frozen with a cryoprobe (-60 degrees C) for periods ranging from 2 to 60 s. The behavioral response to thermal stimulation of the hind footpad was tested pre- and postoperatively at days 3, 5, 7, 9, 13, 15, 19, 22, 26, and 32. In separate groups of animals with similar lesions, nerves were removed and processed for electron microscopy. Light and electron microscopy were used to determine the nature of injury to nerve fibers and its extent. There was a direct relationship between the duration of the freeze lesion and: (1) the number of nerve fibers injured; and (2) the magnitude of the resulting Wallerian degeneration. Following partial sciatic nerve injury with axonal degeneration, hyperalgesia developed within several days, peaked at approximately 1 week postinjury, and resolved during the next several weeks. Both the magnitude of the hyperalgesic response and its persistence were directly related to the duration of the freeze lesion, except in those animals in which all nerve fibers were damaged. These animals were anesthetic to thermal stimulation of the experimental footpad. This relationship helps explain the pathogenesis of painful syndromes associated with failed cryoneurolysis and may be useful in itself as a model of neuropathic pain.

Quantitative neuropathology of a focal nerve injury causing hyperalgesia.

The chronic constriction injury (CCI) model of neuropathy in the rat produces hyperalgesia and allodynia in the sciatic distribution of one hindlimb. We previously described the pathology of the affected nerves at the light microscopic and electron microscopic levels and in this report quantify the morphological changes of the nerves. This analysis gives new insights into the pathophysiology and pain-related mechanisms in this model of human neuropathy. We observed that total fascicular area increased up to fourfold due to an initial massive increase in edema and, later, endoneurial cells. Intact myelinated nerve fibers were reduced from 75% of fascicular area to 29.7% on day 1 and to a minimum of less than 0.5% on day 14 when edema had resolved. The few surviving myelinated fibers were in the small to medium size range. Fiber size histograms revealed an increase in fiber size early on, corresponding to fiber swelling, and the later loss of large as well as small myelinated fibers. Unmyelinated nerve fibers dropped from 19.36/1,000 microns 2 to 6.08/1,000 microns 2 on day 5, and increased from there on. Sprouts were first visible on light micrographs on day 7, occupying 6.8% of fascicular area, while regenerating fibers that were undergoing myelination reached 42.6% of fascicular area by day 42. Macrophage numbers were maximal on day 14 and were still increased on day 42. These data support the hypothesis that the pathogenesis of the extended hyperalgesia following chronic constrictive nerve injury is temporally linked with Wallerian-like degeneration and macrophage activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral nerve pathology following sciatic cryoneurolysis: relationship to neuropathic behaviors in the rat.

Sciatic cryoneurolysis (SCN) is an experimental rat mononeuropathy model that produces neuropathic behavioral sequelae distinct from other neuropathy models. Following SCN, there is limited autotomy peaking in severity and incidence at 7-14 days and delayed but sustained allodynia appearing at about 21 days, with no evidence of thermal hyperalgesia. This study quantified peripheral nerve pathology at weekly intervals following SCN to determine the relationship of nerve degeneration and regeneration to the resulting abnormal behaviors. Fiber histograms based on axon diameter and grid morphometry were used to quantify the pathologic state of nerve fibers, activated phagocytic cells, vessels, and edema at the lesion site. Approximately 90% of the axons demonstrated Wallerian-like degeneration by 3 days post-SCN. At 14 days, small diameter axons significantly increased in number from earlier times following SCN (P < 0.05) but were not significantly different from normal values. At 21 days, the number of small diameter axons was significantly increased over both 14 days (P < 0.05) and normal values (P < 0.05). At 28 days, intermediate diameter axons significantly increased in number with respect to all earlier time periods (P < 0.05). These increases in regenerating fibers overlapped with the development of peak autotomy at 7-14 days and the onset of allodynia after 21 days. Autotomy scores at 7 days positively correlated with grid morphometry data of regenerating axons (rho = 0.7) and activated macrophages and Schwann cells (rho = 0.8) and inversely correlated with edema (rho = -0.8) using Spearman's rank correlation analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathology of experimental compression neuropathy producing hyperesthesia.

An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain-related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light and electron microscopy at different time points from 1 day to 12 weeks after surgery. Edema was the initial pathologic change seen in the neuropathy and was associated with early Wallerian degeneration on day 1. Injury to the connective tissue sheaths with interruption of the perineurial layer, infiltration of macrophages into the endoneurium, and proliferation of endothelial cells were observed during the first week. Endothelial cells hypertrophied and changed to a rhomboid shape with gaps between adjacent cells. Most large myelinated and many small myelinated fibers underwent Wallerian degeneration. Unmyelinated fiber numbers were reduced to one-third of the normal value from day 5 to day 14. Axonal sprouts were numerous after 1 week and grew into the segment distal to the ligatures by 4 weeks. Aberrant sprouts in minifascicles outside the perineurium were present from 4 weeks on. The original ligatures were rapidly surrounded by large amounts of fibrous tissue and mostly absorbed by 12 weeks; the initial fascicular compression caused by the ligatures was maintained by the fibrous tissue. We conclude that, whereas neuroma formation may contribute to the pain-related behavior in the later stages of this neuropathy, acute changes in the endoneurial microenvironment are important for its initial development.

Subperineurial demyelination associated with reduced nerve blood flow and oxygen tension after epineurial vascular stripping.

Using laser Doppler measurements of nerve blood flow and electron microscopy, we determined that removal of the vasa nervorum from the surface of rat peripheral nerve results in an immediate 58.4% +/- (SD) 12.6% reduction in nerve blood flow (p less than 0.017) and subsequent subperineurial demyelination. To further assess the role of ischemia in demyelination, a second group of Sprague-Dawley rats (250 to 300 gm) was anesthetized and oxygen tensions were recorded with platinum microelectrodes in the tibial epineurial and endoneurial spaces before and 30 minutes after epineurial devascularization. Normal epineurial oxygen tension was 40.4 +/- (SD) 6.5 mm Hg before devascularization and 26.3 +/- 12.3 mm Hg after (p less than 0.012). Normal endoneurial oxygen tension was 22.9 +/- 6.0 mm Hg before devascularization and 14.3 +/- 5.4 mm Hg after (p less than 0.003). The topography of nerve fiber injury in this experimental model is identical with the changes induced in the sciatic nerve by circumferential compression at 30 mm Hg which is also thought to impede epineurial circulation. This subperineurial pattern of demyelination and axonal degeneration is associated with experimental interference with the epineurial circulation and may be contrasted with the central fascicular degeneration caused by microsphere embolization of the vasa nervorum via the common iliac artery. The data suggest that ischemia is the mechanism for subperineurial fiber injury after epineurial devascularization and highlight the importance of the transperineurial vessels which connect the epineurial anastomotic circulation and endoneurial capillary network.

Effects of local anesthesia on nerve blood flow: studies using lidocaine with and without epinephrine.

Peripheral nerves have a dual blood supply of intrinsic exchange vessels in the endoneurium and an extrinsic plexus of supply vessels in the epineurial space that cross the perineurium to anastomose with the intrinsic circulation. The extrinsic supply is responsive to adrenergic stimuli. In this study we measured nerve blood flow in rat sciatic nerves with a laser Doppler flow probe. Normal saline, solutions of 1% or 2% lidocaine HCl with and without 1:200,000 epinephrine, or 1:200,000 epinephrine in normal saline were topically applied to the nerves to determine their effect on nerve blood flow. At the end of the subsequent 10-min recording period, blood flow was significantly depressed for all of the solutions tested except saline. Reductions of blood flow ranged from 19.3% for 1% lidocaine HCl to 77.8% for 2% lidocaine HCl with epinephrine. Epinephrine by itself significantly reduced nerve blood flow; when added to local anesthetic solutions, it reduced nerve blood flow to a greater extent than the reduction caused by anesthetics alone. There was an additional significant reduction in nerve blood flow when the epinephrine groups were compared with the pure local anesthetic groups.

Proximodistal gradient in endoneurial fluid pressure.

Endoneurial fluid pressure measurements were made in the interstitial space of rat L5 dorsal root ganglia and in the corresponding sciatic nerves. Endoneurial fluid pressure was always higher in the ganglia than in the paired distal nerve. This proximodistal gradient in endoneurial fluid pressure may be the driving force responsible for the proximodistal convection of endoneurial fluid.

Dose-dependence of endoneurial fluid sodium and chloride accumulation in galactose intoxication.

Endoneurial edema in galactose neuropathy was studied in a colony of Sprague-Dawley rats fed diets containing 0%, 10%, 20% or 40% D-galactose for approx. 200 days. Endoneurial fluid was analyzed by X-ray microanalysis for electrolyte concentration, by microgravimetry of whole nerve segments for water content, by measurement of endoneurial fluid pressure and by morphometry in transverse sections of nerve. Galactose intoxication resulted in dose-dependent increases in endoneurial fluid sodium and chloride that were directly associated with increases in nerve water content and endoneurial fluid pressure. The presence of edema and its dose-dependence was also confirmed by morphometric analysis of sciatic nerves at the light microscopic level. The data demonstrate that electrolyte-induced osmotic imbalances in endoneurial fluid are dependent on the amount of galactose ingested and suggest that the dose-related accumulation of sodium and chloride in endoneurial fluid contributes substantially to the pathogenesis of galactose neuropathy.

Delayed nerve regeneration in streptozotocin diabetic rats.

Nerve regeneration across a 10-mm gap was delayed in streptozotocin diabetic rats 3 and 4 weeks after transecting the sciatic nerve. Opposite ends of each cut nerve were introduced into a silicone tube, leaving a 10-mm gap. Electron microscopy was used to evaluate the progress of regeneration in sections at 2-mm intervals across the 10-mm gap. After 3 weeks, control axons had bridged the 10-mm gap, and myelin sheaths extended for 6-8 mm. By contrast, axons and their myelin sheaths were seen no further than 2 mm from the proximal stump in diabetic animals. By 4 weeks, axons had bridged the gap in diabetics; however, they appeared immature and showed dystrophic changes. The findings suggest that although regeneration does occur in diabetic nerves, it is significantly delayed and qualitatively impaired.

Endoneurial fluid is hypertonic. Results of microanalysis and its significance in neuropathy.

A new technique has been developed for the microanalysis of interstitial fluid from peripheral nerve. Energy dispersive spectrometry (EDS) was employed to measure X-ray fluorescence secondary to electron excitation of endoneurial fluid in order to determine the concentration of sodium, chloride, and potassium from 100 picoliter samples collected in situ. Normal Long-Evans (L-E) rats had endoneurial fluid electrolyte values which were higher than serum values and which explained the positive fluid pressure in peripheral nerve interstitium. Ten weeks after starting a diet containing 6% lead carbonate in powdered laboratory chow, endoneurial fluid electrolytes in LE rats were significantly reduced and approached serum electrolyte concentrations. This change occurred subsequent to angiopathy and increased permeability of the blood-nerve barrier. This sensitive new technique should provide previously unattainable data to assess the pathological role and the dynamics of the nerve fiber environment in relationship to early changes in nerve function.

Characteristics of the ionization tracks and interactions of uranium-238 nuclei in emulsion.

The acceleration and extraction of uranium-238 nuclei by the Bevalac have been confirmed by their visual detection in nuclear research emulsion. A preliminary result for the collision mean free path for stopping uranium-238 (energy

Biophysical and pathological effects of cryogenic nerve lesion.

Changes in endoneurial fluid pressure (EFP) and morphology were studied in rat sciatic nerves frozen for 60 seconds with a cryoprobe designed for human cryoanalgesia. The onset of increased EFP was rapid, and a peak of 23 cm H2O was reached within 90 minutes after injury. EFP levels returned to normal 32 days after freezing. The peak value represents the highest EFP yet recorded in an experimental neuropathy. Microscopic examination revealed severe vascular injury as the probable mechanism of edema, with leakage of horseradish peroxidase tracer at the site of injury and diapedesis of polymorphonuclear cells through vessel walls. Wallerian degeneration was also observed in segments of nerve distal to the site of injury. Analysis of EFP data revealed a biphasic pattern of endoneurial edema: initial marked pressure elevation subsides within hours but is followed by a second peak several days later. We interpret this to suggest superposition of two separate pathological processes following cold injury. At first, extensive vascular damage permits plasma and cellular extravasation, which rapidly increases EFP. Subsequently, nerve fibers undergo wallerian degeneration, a process associated with elevated EFP, which is maximal 6 days after injury.

The renal compression syndrome.

A clinical example of perirenal compression producing documented renin-mediated hypertension is presented. The pathophysiology of this disorder is discussed as it relates to renin release mechanisms. In the future, recognition of the renal compression syndrome may obviate needless nephrectomies since simple removal of the source of compression should result in the cure of hypertension.

Hyperactive boys and their brothers. A 25-year follow-up study.

Twenty men, who had conformed to diagnostic criteria for the hyperactive child syndrome 20 to 25 years ago, and their brothers were interviewed. A large majority of men who were hyperactive had completed high school, and each was steadily employed and self-supporting. Half of the men who were hyperactive continued to show a number of symptoms of hyperactivity. Nearly half had problems of a psychiatric nature and despite normal intelligence quota scores and levels of education, these men had not achieved a socioeconomic status equal to that of their brothers or their fathers. Our findings suggest that emotional problems in everyday living may result from the persistance of symptoms of hyperactivity and that most social and psychiatric consequences of the disorder relate to its presence in childhood as well as to its persistance in adulthood.