Monthly Archives: February 2013

Increase Height And Grow Taller Through Epiphyseal Distraction And Epiphysiolysis

Something that we as researchers have to admit at this point if we are up to date with the amount of research we have already done is that people with growth plates can achieve increased height and being taller much easier than people without their growth plates. Another word to describe the growth plates is the medical term “Physis” and when we are describing anything that is related to the term “physis” we say it is “physeal” or “epiphyseal”.

The 2nd thing the research has almost shown with definite conclusiveness is that distraction will help make the epiphyseal plates increase in thickness faster which translates to the overall human body to make them taller. Distraction, or even wounds in terms of fractures themselves give the bones a chance to either heal or develop pieces of mesenchyme progenitor cells which can lead to the chondrogenic lineage and develop into longitudinal growth.

This post is to see what we have available at this time from studies done to see how effective or feasible is the idea of doing distraction or by applying a tensile load on growth plate cartilage or just the epiphyseal ends of long bones to make them longer, thus make the person taller.

Study #1: Experimental limb lengthening by epiphyseal distraction.

  • Clin Orthop Relat Res. 1978 Oct;(136):111-9.
  • Sledge CB, Noble J.
  • PMID: 729274
Abstract

Kirshner wires were placed either side of the right distal femoral epiphysis and a constant tension device applied a distracting force across the plate in rabbits. Growth increase was measured between the wires and found to be about 150% greater than the concurrent normal growth between 2 control (undistracted) wires on the left; such growth increase can occur in the absence of fracturing. The forces required to do this were between 1/5 and 1/10 of those shown to cause fracturing in vitro. The growth increase was shown to be associated with hyperplasia and hypertrophy of the plate, as well as an increased rate of cell division and sulfated polysaccharide synthesis. This was in turn shown to be associated with an increase in new bone formation.

Study #2: Response of the growth plate to distraction close to skeletal maturity. Is fracture necessary?

  • Clin Orthop Relat Res. 1990 Jan;(250):61-72.
  • Kenwright J, Spriggins AJ, Cunningham JL.
  • Source: Nuffield Orthopaedic Centre, Oxford, England.
  • PMID: 2293946

Abstract

Axial force applied during epiphyseal distraction has been measured close to skeletal maturity in patients having leg lengthening, in a rabbit model, and in vitro from an amputation specimen. In the patient study, both slow distraction rates and low constant distraction loads were applied. For all the distraction regimens, it was not possible to lengthen the limb significantly without evidence of fracture as demonstrated by a sudden decrease in distraction force. Growth plate failure was observed from 600 to 800 N, these levels being lower than those recorded from the in vitro tests. In the animal study, three distraction regimens (0.13, 0.26, and 0.53 mm/day) were applied across the upper tibial growth plate of New Zealand white rabbits close to skeletal maturity. Distraction was applied and force measured using a strain-gauge dual-frame external fixator. The force-time results revealed two distinct patterns. One pattern, in which the forces rapidly increased to maximum values of approximately 25 N and then suddenly decreased, indicated fracture of the growth plate, which was confirmed histologically. In the other pattern, forces increased steadily throughout distraction, reaching maximum values at the end of distraction of approximately 16 N. Histologic observations indicated hyperplasia of the growth plate without fracture, however, only a small increase in limb length was detectable. Hence, if a significant increase in leg length is required close to skeletal maturity, then fracture of the growth plate must occur.

Study #3: Limb lengthening by epiphyseal distraction. An experimental study in the caprine femur.

  • J Orthop Res. 1987;5(4):592-9.
  • Steen H, Fjeld TO, Rønningen H, Langeland N, Gjerdet NR, Bjerkreim I.
  • Source: Sophies Minde Orthopaedic Hospital, University of Oslo, Norway.
  • PMID: 3681532

Abstract

Epiphyseal distraction of the left distal femur was accomplished in 10 goats (aged 3-4.5 months). A modified Hoffmann external fixation device was used as a unilateral distraction frame. A distraction rate of 1.5 mm/day was applied for 5.5 weeks. Epiphysiolysis occurred after 3-7 days of distraction. After the lengthening procedure, the growth plate had reduced in height in eight animals on radiographic examination. In two animals the growth plate was fused. Three animals were killed at 4 (Group 1) and 8 (Group 2) weeks and four animals at 16 (Group 3) weeks after the end of the distraction period. The gain in leg length obtained by distraction was reduced owing to growth retardation in the distal femur of the operated limb. The average final lengthening was 24.9, 19.4, and 13.4% in Groups 1, 2, and 3, respectively. Femur and tibia from both sides were tested mechanically in torsion. Only one femur fractured in the elongation area. All but one elongated femur fractured in the area of the diaphysis subjected to distractional force. The torsional strength of the elongated femur compared with control was reduced to approximately 50% in all groups. The corresponding torsional strength of the tibia on the elongated extremity compared with control was reduced to approximately 75% in all groups. The difference in relative strength of femur compared with that of tibia was statistically significant. This finding can be explained by a stress-protective effect on the femur in the distraction area caused by the external device.

Study #4: Epiphysiolysis as a method of limb lengthening.

  • Clin Orthop Relat Res. 1978 Jun;(133):230-7.
  • Letts RM, Meadows L.
  • PMID: 688713

Abstract

Epiphysiolysis followed by distraction was performed at the proximal tibial growth plates in 18 young rabbits. Union across the distracted plate occurred in all animals. In 12 rabbits skeletally immature at operation, premature fusion of the separated plate resulted in growth arrest of the operated limb. The contralateral control limb was longer at maturity by an average 1.10 cm. In 6 rabbits near skeletal maturity at epiphysiolysis, the operated limb was the longer at maturity by the amount distracted, an average of 0.62 cm. In all animals a permanent loss of joint motion resulted. Epiphyseal distraction in the very young rabbit does not appear to be practical due to consistent premature fusion of the distracted growth plate. It is possible to lengthen the limbs of rabbits near skeletal maturity with this procedure. An added advantage is that union between the epiphysis and the metaphysis always occurred, eliminated the problem of delayed ana non union found in diaphyseal lengthening. However, at this time, until the effects of distraction and compression on the adjacent joint can be minimized, epiphysiolysis as a method of limb lengthening is not recommended in children.

Analysis & Interpretation:

Study #1 seems to show that at least in lab rabbits, when you use steel wires wrapped around the distal epiphysis end of the femur and pull with the force/area or load that is just 1/5th of the amount needed to cause the bone to fracture, you can get the cartilage of the growth plate to increase its growth rate by 150%. The cause of the increased growth is from chondrocyte hypertrophy, hyperplasia, increased cell proliferation, and sulfated polysaccharide synthesis. What is important to note for this study is that the load was increased gradually in tension fashion.

Study #2 is one of the most significant studies yet to show what will probably happen with bone tissue if we tried to stretch out the bones for bone lengthening. However the study was done where the cartilage in growth plates were stretched out, not bones. The researchers were testing the behavior of growth plates for people or lab animals who were close to bone maturity. What is noticed for both situations where either the slow distraction rates and low constant distraction loads were applied, the researchers noticed that if one tried to lengthen the bone significantly the distraction force will reach a certain point before decreasing dramatically. The sudden decrease in the needed distraction force indicates that the pulling motion had caused a fracture in the growth plate. The failure of the growth plate in being able to continue doing plastic or elastic deformation is seen around the 600 Newtons to 800 Newtons level, which I don’t think is all that high in value for a load. It seems that the in vivo results are lower than the in vitro results.

In lab animals, specifically New Zealand rabbits of the 2nd study, the equipment used is a strain-gauge dual-frame external fixator. The rabbits were also close to bone maturity. When the results are graphed in terms of force vs. time, there seems to be two possible patterns seen in the results. Either the process of slowly increasing the tension load up to 16 Newtons while the distraction is done slowly or the process is increased to 25 Newtons rapidly and there is a sudden drop in the load force indicating fracture. The researchers note for a conclusion…

Hence, if a significant increase in leg length is required close to skeletal maturity, then fracture of the growth plate must occur.

If these results can be translated to human subjects, then we can say that the idea of using tension forces to slowly stretch out the growth plate cartilage in teenagers with plates that are almost closed may not be the best idea since it could result in the fracture of the cartilage. It seems that plastic or elastic deformation is a very low possibility, unless there is special equipment that can make the distraction very slow, in terms of maybe only 0.1 mm/day in bone lengthening.

In the 3rd study, the experiment was done on very young goats. There was only 10 goats used in the experiment. I am not sure at this time whether the goats of only 3-4 months years old would have open or closed growth plates but I would assume now that the growth plates were open since the goats were less than 1 years old. There was an unilateral distraction frame used. The rate of lengthening was 1.5 mm/day for 5.5 weeks (or around 40 days). What seems to happen is that the growth plates seem to decrease in length from the distraction. two of the goats actually had the growth plates completely fuse from the distraction.

After the experiment the goats were killed either 4, 8, or 16 weeks after in groups of 1,2, and 3 respectively. It seems that if one waited later to kill the goats, the measured increase in bone length actually decreased from some type of growth stunting. The goats that were killed later showed less bone lengthening. The long bones that were lengthening were also put in a device that would twist the bone to see how much weaker the torsional load strength had become. For most of the goats, the torsion strength after distraction of the femur had decreased to just 50% of what it was before. For the tibia who was put to the torsion load, the torsion strength dropped to just 75% of what it was before. This study is useful to see what would happen to the growth plates and overall bone strength if we tried to lengthen the femur or tibia in people with open growth plates.

In study #4, the long bones in rabbits are first cut at the section between the epiphysis and the growth plates. Then the entire long bone is stretched apart. What is evident from most of the rabbits is that from the epiphysiolysis, if it is done to young subjects, it will lead to premature fusion of the growth plate leading to growth stunting. If the epiphysiolysis is done on subjects which are close to skeletal maturity, the distraction would lead to longer bones compared to control subjects which didn’t have the epiphysis cut apart from the metaphysis. It seems that overall, there is a reducing in the bone joint mobility in all subjects if the cut is done. The researchers note…

“Epiphyseal distraction in the very young rabbit does not appear to be practical due to consistent premature fusion of the distracted growth plate.”

However they do say that the idea of bone lengthening right before the cartilage is completely ossified might be possible but anything before the time of skeletal maturity will only stunt the longitudinal growth of the full long bone.

It is important to note what the researchers say at the very end of the abstract for any orthopedic surgeons who wants to do limb lengthening on children…

“However, at this time, until the effects of distraction and compression on the adjacent joint can be minimized, epiphysiolysis as a method of limb lengthening is not recommended in children.”

 

Growth Acceleration For Children With Open Epiphyseal Plates From Electric Field Application Is Due To Voltage Gradients

In one of the biggest discoveries ever made on our endeavor, I and many other height increase seekers and researchers before me found a Patent “Method for non-invasive electrical stimulation of epiphyseal plate growth” (US 4467809 A) and the PubMed research article which was written with the patent “In vivo growth plate stimulation in various Capacitively Coupled Electrical Fields“. In this post, we go back to the patent and the PubMed article to see if we can look deeper into the references and the related articles associated with Dr. Brighton’s work to see whether there is more information we might be able to gain from studying the published works.

I wanted to go to 3 related studies he had published back in the 70s & 80s which all sort of involved the same basic idea. You apply a constant electrical current and put it close to cartilage or chondrocytes and see what will happen as a result.

Study #1: In vitro epiphyseal-plate growth in various constant electrical fields.

  • Brighton CT, Cronkey JE, Osterman AL.
  • J Bone Joint Surg Am. 1976 Oct;58(7):971-8.
  • PMID: 185224
Abstract

An in vitro epiphyseal-plate model was subjected to various electrical fields. At a voltage gradient of 1500 volts per centimeter, a consistent, highly significant acceleration of growth of the epiphyseal plate occurred as measured from photomacrographs and as indicated by incorporation of 45Ca, 35S, and 3H-thymidine. The growth acceleration was due to voltage gradients and not to current flow. Although the mechanism of action of the electrical field is not known, it is obvious that the voltage gradient, either directly or indirectly, incites a physiological response of the growth-plate chondrocyte.

Study #2: Increased cAMP production after short-term capacitively coupled stimulation in bovine growth plate chondrocytes.

  • J Orthop Res. 1988;6(4):552-8.
  • Brighton CT, Townsend PF.
  • Source: Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.

  • PMID: 2837556

Abstract

Growth plate chondrocytes from newborn calf costochondral junctions grown in monolayer were subjected to a capacitive AC signal of 500 V peak to peak (P-P) at 60 kHz for 48 h and were analyzed for [3H]thymidine uptake. The stimulated chondrocytes showed a 130% greater uptake over unstimulated controls. Other newborn calf growth plate chondrocytes were stimulated at 500 V P-P at 60 kHz for 2.5, 5.0, 10.0, and 20.0 min and were analyzed for cAMP. Chondrocytes stimulated for 2.5 and 5.0 min showed a 142.8% (p less than 0.05) and 394.5% (p less than 0.01) increase over controls, respectively. The chondrocytes stimulated for 10.0 and 20.0 min showed no significant difference from the controls. It is concluded that short-term exposure of growth plate chondrocytes to an appropriate capacitively coupled field stimulates cAMP production, but longer-term application of the electrical field is ineffective.

Study #3: In vitro growth of bovine articular cartilage chondrocytes in various capacitively coupled electrical fields.

  • J Orthop Res. 1984;2(1):15-22.
  • Brighton CT, Unger AS, Stambough JL.
  • PMID: 6491794

Abstract

Isolated articular cartilage chondrocytes from 1- to 3-week-old male Holstein calf knee joints were formed into pellets containing 4 X 10(6) isolated cells and were grown in tissue culture medium (minimum essential medium/NCTC 135) containing either 1 or 10% newborn calf serum (NBCS) in plastic Petri dishes in 5% CO2 and air at 37 degrees C in saturation humidity. On the 4th postisolation day either [35S]sulfate or [3H]thymidine was added to the medium, and the pellets were exposed for 24 h to capacitively coupled electrical fields (10, 100, 250, and 1,000 V peak-to-peak, 60 kHz, sine wave signals). The pellets were then harvested, dialyzed, hydrolyzed, and assayed for DNA, protein, [35S]sulfate incorporation, and [3H]thymidine incorporation. Results indicated that at 250 V peak-to-peak there was a statistically significant increase in [35S]sulfate in 1% NBCS and a statistically significant increase in [3H]thymidine in 10% NBCS. At potentials above or below 250 V no changes were noted. Thus, articular cartilage chondrocytes grown in pellet form can be stimulated to increase glycosaminoglycan synthesis or to increase cell proliferation by an appropriate capacitively coupled electrical field. The importance of the serum concentration in the medium in evaluation of biosynthesis in vitro is noted.

Analysis & Interpretation:

I had already used these studies before in previous posts but they were from many months ago when my knowledge on the subject and the research was still very superficial in nature. This time around I am going to try to go deeper on the details and understand at a deeper level what the implications and applications would be for the results of the studies.

Study #1 is the one that we see has the most interesting of results, at least in the abstract. When we apply a voltage gradient, then the epiphyseal plate cartilage seems to increase in its growth. Since the set up is in vitro, I do wonder just how one tests growth plates in an in vitro setup. Is the growth plate explanted from the test animal?

It is important to note that the growth of the cartilage is from the voltage difference, not from current flow. The optimum gradient they found was 1500 Volts/cm. The term “gradient” refers to differences between two points of some unit in concentration. A Voltage gradient means that if one measured the voltage with two electrodes with one of the electrodes kept in one place, and the other electrodes measured at difference lengths of the growth plate thickness or length, the voltage values relative to the set point would be changing. The growth plate’s increased growth is found through testing using Calcium, Sulfur, and Thymidine, and a type of imaging technique known as photomacrographs. The actual mechanism of how the applied electrical field actually works to increase growth plate increased growth is not known but the conclusion made by Brighton is that the voltage gradient created when the electrical field is generated is what will directly o indirect stimulate the chondrocytes.

In Study #2 we see that instead a DC current created a steady state electrical signal, Brighton tried to use an AC signal instead to see what would happen. The researchers took growth plate cartilage from a newborn calf’s ribcage area and put the chondrocytes in a monolayer structure. The AC electrical signal is induced at 500 Volts for the amplitude and the frequency being 60 Hz. The field is applied for 2 days (48 hours) and the chondrocyte concentration was tested by using thymidine uptake. There was a 130% increase over unstimulated chondrocyte controls. So the researchers tried the AC electrical field stimulation to test to see whether the chondrocytes would show increased cAMP production. When the 500 Volt amplitude, 60 Hz signal was applied, the 10 min & 20 min duration showed to increased cAMP production increase, but the 5 min and 2 min did show increased cAMP increase. This shows like so many other stimulants, if we want to make the chondrocytes in growth plates increase in cAMP production, which is one of the things we will need to do to make chondrocytes go faster, we have to have a optimum duration time for electrical signal stimulation. The optimum seems to be just a short term, 5 min. round which would increase the cAMP production by over 4 times.

In study #3 brighton ans other researcher took chondrocytes from newborn calf knee joints. The chondrocytes were put in pellets with the concentration of chondrocytes around 4,000,000 in each pellet. The pellets were grown in a tissue culture medium with different concentrations of calf serum in petri dishes. In 4 days after the chondrocytes were separated from the calf, the thymidine and/or the sulfate was injected into the culture. Then the capacitative electrical field was applied. The variable that was changed was the amplitude of the sinusoidal signals, which ranged from 10 volts to 1000 volts. The frequency was 10 kHz and the duration was 24 hours. Afterwards the pellets were taken, and treated to test to see how much DNA, proteins, sulfate uptake, and thymidine uptake the chondrocytes had done. With the 1% newborn calf serum in the culture, the 250 Volts led to a high sulfate uptake by the chondrocytes while the 10% newborn calf serum in the culture had the 250 volts cause a very high uptake of the thymidine. The researchers conclude with…

Thus, articular cartilage chondrocytes grown in pellet form can be stimulated to increase glycosaminoglycan synthesis or to increase cell proliferation by an appropriate capacitively coupled electrical field.

The implications and main things we should take away from the studies we just took at is the idea that we can easily create a device that can produce either the DC or AC electrical signals we need at the high voltage amplitudes and the frequencies we need to stimulate either the articular cartilage chondrocytes or the epiphyseal growth plate chondrocytes. If we can get any type of mesenchyme in the bone to differentiate into chondrocytes, the application of the right duration and voltage gradient of capacitative electrical signal would mean that the chondrocytes might start proliferating, which could result in even adults with no growth plate cartilage to develop cartilage again.

The Principles On Using FGF-2 To Induce Articular Cartilage Regeneration

The idea of using the growth factor FGF-2 and the need to understand how we can induce articular cartilage regeneration has been a couple of consistent topics I have brought up over and over again in this website. The FGF-2 aka Fibroblast Growth Factor has been one of the best candidates that is known at this time which can help the human body in vivo generate some type of cartilage-like tissue which we would definitely need to be added into the bone to remodel it in any way longitudinally. I wanted to summarize 4 PubMed studies I’ve found which show in either a direct or indirect way how effective using the FGF-2 growth factor is in getting cartilage to be formed.

Study #1: Differentiation of chondrogenic precursor cells during the regeneration of articular cartilage

  • Y. Hirakif1, C. Shukunami, K. Iyama, H. Mizuta
  • Department of Molecular Interaction and Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto; Departments of Surgical Pathology and Orthopedic Surgery, Kumamoto University School of Medicine, Kumamoto, Japan

Abstract

Objective: Full-thickness defects that penetrate articular cartilage are filled by fibrous, or fibrocartilaginous tissue and, to a very limited extent, also by hyaline cartilage. In rabbits, small full-thickness defects (to ≤53 mm in diameter) are capable of regenerating surfacing hyaline cartilage. However, chondrogenic differentiation does not occur in larger defects (≥5 mm in diameter). We studied the involvement of fibroblast growth factor-2 (FGF-2) in the cartilaginous repair response in full-thickness defects of articular cartilage in vivo, and attempted to facilitate cartilaginous repair of the defects by the local administration of FGF-2.

Design: The right knee joint of male adolescent Japanese white rabbits was entered through a medial parapatellan approach, and the patella was dislocated laterally to expose the articular surface of the femoral trochlea. Full-thickness defects were created in the weight-bearing area of the femoral trochlea with a hand-drill (the 5-mm diameter defects in 80 rabbits and the 3-mm diameter defects in 40 rabbits). The animals were fitted with an osmotic pump connected to silastic medical grade tubing, and a length of the tubing about 5 mm long was introduced into the articular knee cavity. The 5-mm-diameter defects received FGF-2 (50 pg/h) or sterile saline via an osmotic pump for the initial 2 weeks. Five animals each were sacrificed after 1, 2, 4, 8, or 24 weeks after creation of defects. The 3-mm diameter defects received a neutralizing monoclonal antibody against FGF-2 (50 nglh) or pre-immune mouse IgG (50 nglh) for the initial 2 weeks. Five animals each were sacrificed after 2, 3, or 4 weeks after creation of defects. The distal portion of each femur was removed, fixed, decalcified, and embedded in paraffin for the subsequent histological analysis. Sections were cut in the transverse plane, and histologically examined.

Results: The administration of FGF-2 (50 pg/h) resulted in successful regeneration of articular cartilage and the subchondral bone within 8 weeks after creation of 5-mm diameter defects. In these defects, undifferentiated mesenchymal cells initiated chondrogenic differentiation coupled with replacement by subchondral bone, resulting in the resurfacing of the defects by hyaline cartilage and the recovery of subchondral bone up to the original bone-articular cartilage junction. In contrast, the administration of a neutralizing monoclonal antibody against FGF-2 clearly interfered with the action of endogenous FGF-2 in 3-mm diameter defects, which were filled with fibrous tissue. None of the antibody-treated defects were covered with cartilage. We then assessed the proliferative capacity of the undifferentiated mesenchymal cells in the defects by immunostaining the proliferating cell nuclear antigen (PCNA) at 1 week after creation of defects. The capacity of reparative tissue to form cartilage was well correlated with the occurrence in the defects of a cell population that was PCNA-positive, undifferentiated, and capable of self-renewal.

Conclusions The local administration of FGF-2 resulted in the successful resurfacing of large (5 mm in diameter) defects by hyaline cartilage. Prechondrogenic mesenchymal cells were the likely targets of FGF-2, which probably promoted the formation of cartilage by stimulating a selective expansion of chondroprogenitor cells. Thus, activation of FGF-2 signalling is critically important for the induction of cartilaginous repair response in full-thickness articular cartilage.

Study #2: One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits

  • H. Chuma, M.D.†,  H. Mizuta, M.D., Ph.D.†, S. Kudo, M.D., Ph.D.†, K. Takagi, M.D., Ph.D.†, Y. Hiraki,Ph.D.‡
  • † Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
  • ‡ Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

Summary

Objectives

Administration of fibroblast growth factor (FGF)-2 for 2 weeks induces a successful cartilaginous repair response in 5-mm full-thickness articular cartilage defects in rabbits. The purpose of this study was to investigate the effects of a short time exposure to FGF-2 on the repair of the defects.

Methods

Five-mm-diameter cylindrical defects, which do not repair spontaneously, were created in the femoral trochlea of the rabbit knees. The defects were administered sterile saline or FGF-2 (150 pg/h) via an osmotic pump for the initial 1 day, 3 days, or 2 weeks, and we assessed the FGF-2 action on the proliferation and migration of mesenchymal cells in the reparative tissue. Using a total of 126 rabbits, we performed three sets of experiments. We also studied the effect of FGF-2 on migration of marrow-derived mesenchymal cells in vitro.

Results

FGF-2 treatment for 1 day or 3 days induced the sequential chondrogenic repair responses that led to successful cartilaginous resurfacing of defects within 8 weeks as well as the 2-week treatment did. We confirmed by a radioisotope study that FGF-2 injected was rapidly eliminated from the defects (a residual ratio of 50% within 30 min). The effect of FGF-2 on cultured marrow-derived cells suggested that FGF-2 facilitated the mobilization and migration of replicating mesenchymal cells from bone marrow.

Conclusions

Only 1 day exposure to FGF-2 is sufficient for induction of the chondrogenic repair response in 5-mm-diameter full-thickness defects of articular cartilage in rabbits. FGF-2 stimulated the recruitment of mesenchymal cells into the defects, which was a limiting step for the induction of cartilage.

Study #3: Fibroblast growth factor-2 promotes the repair of partial thickness defects of articular cartilage in immature rabbits but not in mature rabbits

  • Tetsuya Yamamoto†, Shigeyuki Wakitani‡, Kazuhiko Imoto†, Takako Hattori§, Hiroyuki Nakaya§,Masanobu Saito†, Kazuo Yonenobu†
  • † Department of Orthopaedic Surgery, Osaka-Minami National Hospital, Kawachinagano, Japan
  • ‡ Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
  • § Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan

Abstract

Objective

To investigate cartilage response to fibroblast growth factor-2 (FGF-2) with increasing age in vivo, we examined the effect of FGF-2 on partial thickness defects of immature and mature rabbits.

Design

Sixty-nine Japanese white rabbits (34 immature rabbits, 35 mature rabbits) were examined. We made experimental partial thickness defects in articular cartilage of the knees. Then, we injected FGF-2 into the knees eight times, immediately after surgery and every 2 days for 2 weeks. A single dose of FGF-2 was 10 ng/0.1 ml or 100 ng/0.1 ml. In the control group, 0.1 ml saline was injected on the same time schedule. The rabbits were sacrificed at intervals following surgery that ranged from 2 to 48 weeks. The specimens were stained with toluidine blue and examined microscopically. We used a modified semiquantitative scale for evaluating the histological appearance of repair.

Results

In immature rabbits, the cartilage repair in the FGF-2 (100 ng)-treated group was significantly better than that of the other groups. The defects were almost completely repaired with chondrocytes that showed a round to polygonal morphology, and large amounts of extracellular matrix with intense metachromatic staining.

In mature rabbits, however, there was apparently no effect from FGF-2 in either group.

Conclusions

Application of FGF-2 facilitated cartilage repair in partial thickness defects in immature rabbits, but not in mature ones.

Study #4: Regeneration of articular cartilage defects in the temporomandibular joint of rabbits by fibroblast growth factor-2: a pilot study

  • H. Takafuji, T. Suzuki, Y. Okubo, K. Fujimura, K. Bessho
  • Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, 54 Syogoin, Kawahara-cho, Sakyo-ku, Kyoto-shi 606-8507, Japan

Abstract

The purpose of this study was to investigate the therapeutic usefulness of fibroblast growth factor-2 (FGF-2) in rabbit temporomandibular joints (TMJ) with osteoarthritis. A 10-mm3 defect was bored in the surface of the mandibular condyle head. The animals were divided into four groups: two test groups in which the defect was filled with lyophilized collagen containing 0.1 or 1.0 μg of FGF-2, and two control groups, in which the defects were filled with lyophilized collagen without FGF-2 or left empty. The defective sites were examined under a light microscope 3 weeks after surgery. Initiation of cartilage formation was observed in the defects filled with 0.1 μg of FGF-2, but only a small amount of cartilage was found in the defects of the 1.0-μg FGF-2- treated group. In the control groups, soft-tissue repair only or no tissue repair was found. In vivo, a dose of 0.1 μg of FGF-2 can stimulate articular cartilage restoration in defects of the TMJ in rabbits, although determining the effective concentration range of FGF-2 may be difficult. The present results suggest that an optimum concentration of FGF-2 could restore defects of TMJ articular cartilage clinically.

Analysis & Interpretation:

From studies 2 & 1, we see that the FGF-2 application on induced articular cartilage defects even up to 5 mm in diameter in area can lead to some type of cartilage repair. Study 1 suggest that not just fibrocartilage can be generated, but even the hyaline cartilage which articular cartilage is made of can be restored back. Not only that, the prochondrogenic progenitor mesenchymal cells seem to be the ones that are really affected by the FGF-2 and they only seem to differentiate in the chondrogenic lineage. The subchondral layer underneath the articular cartilage is also healed as well, and any mesenchymal stem cells that leak from the bone’s intermedullary cavity seem to be pushed towards the chondrogenic lineage. Study #2 agrees with the stimulating ability and function of the FGF-2 but also adds that even one administration of FGF-2 is enough to see chondrogenic results. The FGF-2 seems to be able to stimulate the mesenchymal stem cells to even start moving towards the defect in some mobile fashion.

Study #3 only states that when young test subjects are given the FGF-2 for cartilage repair in comparison to older subjects, the FGF-2 has a far more effect ability in cartilage regeneration ability. Older subjects had almost no cartilage regeneration response but younger testing animals had a much better result. This study was important in showing that like so many other treatments for medical repair or cosmetic enhancement, older test subjects have a far less chance of getting the benefits of treatments.

Study #4 shows that when the FGF-2 was used in application on lab rabbits on the temporomandibular joints (TMJ) area, it seems to show that there might be an optmum amonut of FGF-2 administration for highest level of articular cartilage repair. This study is important to show that the idea of using more FGF-2 is not always better. When the 4 groups were divided with two groups being the controls, it was seen that 0.1 micrograms of FGF-2 was better than 1.0 micrograms of FGF-2 in repairing the articular cartilage in the temporomandibular joint (TMJ) of the rabbits.

Does Praying Or Wishing To Grow Taller Really Increase Height And Make You Taller?

I remember Sky (from EasyHeight.com) once saying in a post of how his daily schedule goes that he would pray each night to his personal God for the strength and power to make the next day better and I wondered whether the power of prayer or wishing would have any influence on a person’s growth. Did Sky also wish for his body to transform to make himself taller?

I have looked through the updates on the website that is now no longer available and it seems that after 4-5 years of trials and doing bone lengthening stretches and pulling using weights, sprinting, and jumping he never increased at all in height. For all the desiring, wishing, and personal determination, dedication, and persistence, he never increased his height by even 1 inch.

I have thought about the issue of whether a person can use will or desire to make their bodies longer. There are some interesting cases we have found where the mental powers seemed to have some effect but the majority of people who express a desire, or even a strong obsession sees nothing results.

I would say that maybe when we still have our growth plates’ cartilage, we might be able to change our state or emotions to become slightly more positive and better to optimize the natural growth rate our genetic pre-programmed. There is already some studies which show that having a negative outlook on life will affect the immunity and health of a person who is still growing and possibly lead to more incidents of illness, which results in stunted growth and increased bone mineral density.

If we can use wishful thinking and praying, we might be able to increase our immune system, and nervous system to relax more, decrease stress, decrease illness, and optimize the natural growth rate. However, I don’t think it is possibly after the cartilage in our growth plates are gone to be able to use just our minds in terms of praying and wishing to increase our height.

There has been no documented cases which showed that through mental exertion or mental manipulation alone can the individual change or remodel the bones in their body, even in terms of increasing the bone mineral density. A female in her 50s can not wish to decrease her chances towards osteoporosis and bone fractures, but needs to implement some type of exercise program and eat more vitamin D based foods to strengthen and remodel her bones internally to be healthier.

There is a case to be said for the strange fact that Dr. Milton Erickson famously had a patient which supposedly increased their height by 12 inches in one year after therapy sessions with him. I wrote about this case in one of the earliest posts entitled “Milton Erickson’s Legend of 12 Inch Height Increase”.

It involved Dr. Erickson making the guy change his perception on how he viewed the world. However this case is well documented and has been going around the internet space and NLP community for the last 5 decades ever since the case was documented in one of his written books. At this point, I would guess instead that the person who was said to be 20 years ld when Dr. Erickson treated him still had the cartilage in his bones and through some relaxation method, he experience a rare case of “catch-up growth” which I wrote about in the post ”
Catch Up Growth Explained, Can We Use It To Increase In Height And Grow Taller?”

So it might be possible with a very good hypnotherapist or NLP expert to get a person to change their state or perception of the world to help increase the growth rate of a person who still have their growth plates, but there powers to change the mind would not work on a person who doesn’t have their growth plates.

Could The Secret To Peak Performance Coach Anthony Robbins Be His Height And Size?

I have talked about the Peak Performance Life Coach Anthony Robbins at least a few times in the span of this website. This is not just because Robbins has a very interesting case of having Gigantism but also because I have been listening and reading his material for a few years now.

There is no doubt that Robbins is very good at what he does which is to facilitate and assist people in reaching their goals and having success in life. However I have always wondered how it was possible that Robbins would be able to achieve success so quickly. I have read the books about this guy and many people have tried to guess at how he was able to succeed so quickly.

In Robbins’ biographies, it documents that Robbins went from total financial ruin to making over $1 million a year in just one year after he decided one night to stop feeling sorry for himself and went for a physically demanding run. All of this was done when he was still in his early 20s. When he was just 19-20, he was already well known as a type of instant-fix psychiatrist.

Many people have wondered what could be the secret to Robbin’s success. Some claim that he understood the NLP principle of Modeling and applied that one step towards everything in his life. He would find the most successful people in the area he wanted to learn, figure out what they were doing, and emulate the characteristics of those successful people.

Others say that he was just at the right place and right time to start what we now would call the “Self Improvement” or “Personal Development” community in the 70s-80s. Of course the ideas for self improvement has been around forever since the time of Dale Carnegie, Napoleon Hill, James Allen, etc but it was Anthony Robbins who would bring the idea of C.A.N.I. (Constant And Never ending Improvement) to the public’s awareness. He decided to take the platform of TV and broadcasted his face and message every night on those late night Informercials in the 80s. He became a national and international start with a very recognizable face.

Besides his drive towards succeeding, he also had a few key mentors and lucky breaks…

  • His meeting and being trained by Grinder, one of the two original creators of NLP.
  • His mentoring by one of the earliest people in the self help industry, Jim Rohn.
  • His initial drive, motivation, and passion to read over 700 books.
  • His chance meeting with Tolly Burkan gave him the idea to incorporate fire-walking into his seminars and programs. The firewalking is an analogy to express the idea that a person can use their mental state to resist pain and overcome their fears 
  • His early wins in life like interviewing Howard Cossell and being able to be proactive in finding his role models.

I am not to take away Robbin’s own hard work in reaching where he was but it is clear that his meetings early on with some influential people in the Self Help community contributed to his fast rise to financial freedom and business success.

However I wanted to make an interesting argument in this post. It is that “I believe the main reason Anthony Robbins has been able to achieve the type of success he has enjoy at this magnitude for the last 3 decades is primarily because of his size/height”

Note: Now it is absolutely true that there are plenty of people in the USA and other countries who most people would consider “tall” or even “giants” but end up broke, a failure, and homeless. I know of even a 7′ 4″ homeless guy who lives on the streets of Portland, Oregon. Being tall does not immediately translate to professional and financial success. Winning the genetic lottery is note enough these days to gaurantee any type of success.

I once heard one self help guru say that for one to truly development into a person that attracts people, one of the 5 key things one must have or develop is presence. Being fully present is very important to develop deep, meaningful relationships with people and have a good communication between people.

When I look at the idea of presence, I can think of only a few things or characteristics which would be used to describe a person who has presence. The words would be magnetic, charming, intense, energy, passion, figure, size, height, gazing into the eyes, warm, etc.

Many people these days want to become “life coaches” which is sort of like therapy but only without the 10 years of medical school training. These jobs are relatively easy with the coach helping their clients figure out their life’s blueprint. It also makes the person who is a coach feel good about themselves since they are “helping other people”. The connection one person makes (as well as the positive emotions they get) in being able to help possibly solve the emotional and psychological issues of another person is very strong. It also helps that a coach is usually very well paid, around the $50/hr range for coaches who start out and that is just for a weekly phone call to their clients. In my opinion, the whole field of “life coaching” is filled with scams and frauds who claim that they are coaches but don’t even have their own lives in order. However, we are talking about one of the most famous, well paid, and most well known “coaches” in the world, if not the one person who actually started this entire sector of society.

I am not going to question at the educational or credentials of Anthony Robbins since coaching has almost always focused on results. Robbins himself only has a High School education but he claims that he has read close to 1000 books in his lifetime to answer one fundamental question which is “What is the difference between the person who succeeds in life and the person who does not?” I guess that is good enough if he can really help people quickly and the clients feel like they really got their money’s worth.

Anthony Robbins clearly has learned the tools needed for success. He learned from the best in his time, and has integrated the ideas into his own system of coaching. He has written two best selling books (“Unlimited Power” and “Awaken The Giant Within”) which many people have said changed their life for the better.

Robbins has said that when he started high school, he was only around 5′ 2″-5′ 3″. Within just 2-3 years, he would have his height shoot up to 6′ 7″. It would be until later in life would he learn that the reason for his insane growth spurt was because of a tumor in his head. We know this as the release of somatropin into his body by the anterior part of his pituitary gland.

After getting medical advice from his physicians around the age of 30, he decided not to operate on the brain and he has been fine since which might indicate the tumour shrunk down after he past puberty. From looking at his face, it seems that the growth hormones have given him the large cheekbones, jawline, teeth, and hands that are characteristic of acromegaly. His body is proportional, and video of him back when he was in his 20s in the 1980s show that he was very fit and healthy.

I think the reason he has reached the success he has is from his ability to use the principle of presence to the maximum, but especially the element of him being so big to generate the element of presence to a very high degree. His combination of passion and energy and warm is something that most people can generate. I have met life coaches which have his level of intensity in life and have just as good speaking and coaching skills. However these people are not at his level of success.

Is it just because Anthony Robbins came before these guys and he was the one who created all of these ideas and systems which the newer coaches are using? i would say partly.

Extreme human tall stature has always generate awe, admiration, and instant respect within humans. I would guess that the behavior of being in awe of taller beings is something that is very instinctual in humans. The fact that Robbins stands 6′ 7″ due to his lucky break in developing gigantism in his teenager years, before his growth plates closed allows him to almost automatically generate respect when an average sized human meets him.

6′ 7″ is over 2 meters and this height is within the 00.1% of all humans in the world. Most people have stated that the first time they meet Robbins is a very unique experience since it is very unusual to meet someone his size. In additon, the growth hormones also made his voice very deep due to the cartilage his larynx thicker generating an automatic deeper voice. Studies in evolutionary psychology has shown that human males with lower, deeper voice tones tend to exhibit more dominant male behavior.

So it would be Robbins asset of his large body size and his deep voice which would make people instantly listen to him speak and assume that he is someone important and influential. In addition, when Robbins was young, even before his insane growth spurt, he was known by his high school friend to be a great speaker, a problem solver, and a communicator. The lowering of his voice which commands more respect due to the cartilage in his trachea and larynx being enlarged helped him develop a even more alpha-like, masculine presence.

This is why I think Robbins has reached the level of success that he has.

If he was a normal sized male, like 5′ 11′ he would still be successful and probably would have become a millionaire after 10 years of hard work, with the type of energy and passion that is his trademark behavior. However I doubt that Robbins would have been able to reach the level of his success so quickly without his height and size. I know rationally and logically that getting a talk from a talk and advice from a big person should be no different from a small person, but at an unconscious level I might be able to take the advice of a small person as seriously and actively as from a person who would be much bigger. Bigger people are just able to command attention and respect so much easier than smaller people.

I personally just can’t imagine a 5′ 3″ Anthony Robbins being able to come up on stage in front of 10,000 people in one of his seminars and still be able to command the same level of respect. He might be the center of attention and his usage of psychological tactics to make people easier to influence might work in his seminars but if he decides to meet his clients face to face for personal coaching, I would say that the ability and quality of his coaching would not be as effective or strong as where he is so much bigger than other people.

This is my two cents on the subject of one of my personal heros and mentors, Anthony Robbins.

Could Giants Found In Legends, Myths, And Stories Really Have Existed In Human Past History?

Something that I have always been curious about is to ask whether the stories, legends, and myths of which we hear about human like giants from past history could really be true. When I was younger, I was absolutely fascinated or even a little obsessed with the occult, esoteric, the paranormal, and the supernatural.

I recently was bored not being able to sleep and I came across an interesting documentary from Youtube which seems to suggest the theory that giants really did exist in human history’s past.

In this post, I will be using and outlining all the important information found from the YouTube video of a documentary done on giants or extremely tall statured Human-like beings. It is “ANCIENT GIANTS existed – Best Full Documentary-HD”. The video uploader goes by the name “Endza50·”. The entire video uploaded to Youtube is around 50 and a half minute long.

It would seem that throughout history people have been telling stories about super-tall human like beings. The most famous giant would be from the bible with Goliath. What some people might not know is that Goliath was actually 1 of 5 brothers and he was part of a group known as the Philistines.

Even in the most published book in human history, the Holy Bible, there is verses which talk about the fact that when the human race was in its infancy, there were giants that roamed the earth. Ex. Chapter 6, Verse 4.

So are we supposed to believe in these ideas of ancient races of extreme tall statured humans up to even 20 feet tall which roamed the earth?

Side note: In the story from the Bible, David did not actually kill Goliath with his sling, but only stunned Goliath enough to make him fall down and knock him to a daze long enough so that David took Goliath’s weapon and then cut off his head.

In the documentary, which I watched with a level of scepticism, it seems that the Mayans and Incans both held beliefs in the legend or myth that a race of giants giants existed before their civilization which would be extinguished by a great flood. They viewed these giants before them as gods and created stone figures in the shape of these giants.

It seems that one of the most common features found in giant skeletons found even in the Northeastern Region of the USA was that they had double rows of teeth. This seems to be one of those things that would be written again and again in any newspaper clippings one finds from the 19th and early 20 century which reported these cryptozoological skeleton findings. Sometimes there is also claim that the giants had 6 fingers and 6 toes.

One speaker named Jim Marrs says that there is a legend made by the Paiutes, a native american tribe indigenous to the Nevada region. From the blog HERE…

The Legend

The Paiutes, a Native-American tribe indigenous to parts of Nevada, Utah and Arizona, told early white settlers about their ancestors’ battles with a ferocious race of white, red-haired giants. According to the Paiutes, the giants were already living in the area.

The Paiutes named the giants “Si-Te-Cah” that literally means “tule-eaters.” The tule is a fibrous water plant the giants wove into rafts to escape the Paiutes continuous attacks. They used the rafts to navigate across what remained of Lake Lahontan.

According to the Paiutes, the red-haired giants stood as tall as 12-feet and were a vicious, unapproachable people that killed and ate captured Paiutes as food. [Overestimation is to be expected.]

The Paiutes told the early settlers that after many years of warfare, all the tribes in the area finally joined together to rid themselves of the giants.

One day as they chased down the few remaining red-haired enemy, the fleeing giants took refuge in a cave. The tribal warriors demanded their enemy come out and fight, but the giants steadfastly refused to leave their sanctuary.

Frustrated at not defeating their enemy with honor [underestimation is to be expected], the tribal chiefs had warriors fill the entrance to the cavern with brush and then set it on fire in a bid to force the giants out of the cave.

The few that did emerge were instantly slain with volleys of arrows. The giants that remained inside the cavern were asphyxiated.

This story seems to have originated by a ethnic Paiute named Sarah Winnemucca (later added the last name Hopkins probably signifying she married a white man) who wrote a book about the history of her people entitled “Life Among the Piutes“.

The whole documentary was very interested and a few very notable, but more infamous writers of the paranormal and conspiracy theorists like Erich Von Daniken, Bruce Rux, David Childress, Brad Steiger, and Jim Marrs all tell some type of anecdotal story showing that the USA short history, many people in the 19th century claimed to have dug up skeletons which are of people who are of extremely tall stature. During the 19th century, the white settlers would go into the midwest and find big mounds which was believed by some local native americans to be graves of ancient giants. When the white settler’s excavated and dug up the mounds to see what was inside, they did seem to find 7-10 feet tall skeletons inside.

A famous case if when men in Bridal Veils Falls, California supposedly found a wall filled with ancient writings. They broke the wall hoping to find gold and treasure but found instead a tall female skeleton holding onto a baby. It seems that similar findings are also in Texas and Nevada. Not just in the USA, during the 19th century, anyone with a shovel was digging into the ground and people fond giant skeletons also in Greece, the Middle East, Turkey, and many other countries around the world.

The 2nd famous case is when people in 1912 went to a cave in Lovelock Nevada to get bat guano but instead found duck decoys, baskets, hunting & fishing equipment, and mummified red-haired giants around 6’6″-7’0”. Sarah Winnemucca in her book tells of this story and that the giants with red hair came from that specific cave. It is said that the people who excavated the cave manage to bring 60 skeletons out of it but none are found today.

giant carving south americaIn South America, besides the Nazca lines, there are other large carved figures like the picture to the right.

The documentary makes a very big push in making the viewer think that there is a high possibility that giants did exist in human’s past.

If I was to make a guess, I would say that it is not unreasonably to believe that maybe there were tribes in human history who chose to selective breed their people for tall stature, to give them a sort of physical edge against their neighbors who might be warring with them. Tall stature has been associated with increased strength and power, and there might be people who have tried in history to get the tall people in their tribe to breed and then after a few generations, the average height of the entire tribe increased. When these tribes then faced warring outsiders, the outsiders would see these people who are so much bigger and be intimated by their size and run away.

While I am sure that a good size percentage of all the documented and written stories throughout hisotory about giants skeletons were hoaxes and scams done by people to have fun or cheat people out of money, it is a little hard for me to believe that all of the cases about giants skeletons were hoaxes. I would assume that at least one of the stories was based on true findings, and that would be enough evidence to show that in human history, there were some groups of people who ended up being much taller than the other groups of people/tribes around them.