Multiple Symmetric Lipomatosis
Multiple symmetric lipomatosis (MSL) is a rare disease first described by Brodie in 1846(1). Madelung reported data on 33 cases in 1888(2), but the classical description of the disease is attributed to Launois and Bensaude who published a detailed account of 65 cases in 1898(3). The literature on MSL is dominated by research on alcoholic men with a reported incidence of 1/25,000 in the Italian population(4). Nonalcoholics and women are also affected(5-7). Over 270 cases are reported in the literature with an age range varying from 20 to 71 years; two cases have been reported in children(8, 9).
Individuals with MSL have increased fat, usually in a symmetrical distribution either on the neck, upper back (buffalo hump) or interscapular region, on the upper arms or chest, in the mediastinum or thighs, sparing the distal limbs(10). The fat in MSL is thin and watery when removed by needle biopsy unless the individual has undergone numerous liposuction or excision surgeries. When transporting fat in media, the fat will stick to the top of a polystyrene container distinguishing this fat from AD or FML. Because the appearance and location of the lipomatosis can vary, MSL has been divided into three types:(6, 11): TypeI or diffuse lipomatosis of the neck (‘horsecollar lipomata’); Type II or multiple symmetric lipomata of the shoulder girdle, the upper arms, the thorax, the thighs and sometimes the abdomen giving the patients the so called ‘pseudoathletic’ appearance; and Type III or a rare type with preponderance of the lipomatosis in the thigh girth (‘gynecoid type’). Women tend to have Type II and III(10).
Associated disorders include liver disease, hyperlipidemia including elevated high density lipoprotein (HDL) levels (in patients with a history of alcohol use), hypertriglyceridemia, hypothyroidism, diabetes mellitus, and neurological changes(12). MSL is an inherited disorder associated with mitochondrial mutations in a few familial cases,(13, 14) however, Klopstock et al.(15) found mitochondrial mutations in only 2 of 12 patients studied. In addition, Chalk et al. found no mitochondrial pathology or mutations in four siblings with MSL with a pattern favoring autosomal recessive (16).
Morbidity and mortality in MSL is high with sudden non-coronary death accounting for a large percentage of deaths in one series.(5) The neuropathology of MSL is a distal axonal demyelination different from that associated with alcohol intake(12, 16, 17) and impairment of autonomic function has been suggested as a possible cause of sudden death; this impairment seems to be prevalently parasympathetic and not related to a high alcohol intake.(18, 19)
Adipose stem cells from MSL tissue express uncoupling protein (UCP)-1 similar to brown adipose tissue, but fail to increase UCP-1 in response to noradrenaline even though MSL cells express b1-, b2- and b3-adrenergic receptors (AR)(20). In agreement, catecholamines did not induce lipolysis in MSL cells as measured by glycerol release.(21) Because a-AR were not evaluated in this study, these data suggest either a dysregulation in b-AR in the MSL tissue or elevated levels of a-adrenergic receptors.
Adipose tissue express endothelial nitric oxide synthase (NOS)(22) and inducible NOS (iNOS).(23, 24) Noradrenaline did not stimulate expression of iNOS in MSL cells, however, a NO donor inhibited proliferation of these cells and a selective inhibitor of NOS stimulated proliferation. These data suggest a normal response of MSL tissue to NO but defective sympathetic signaling. The sympathetically inducible protein PGC-1, involved in mitochondrial biogenesis in brown adipose tissue (BAT) and other cell types(25), was also not stimulated by noradrenaline in MSL cells as in BAT from rats, supporting a defect in sympathetic nervous system stimulation of MSL tissue(20).
In our survey of 110 individuals with AD, we asked specifically about excess fat on the upper back called a ‘buffalo hump’. Twenty-five (22.7%) individuals had positive responses and 80% of these described the fat as painful. The presence of a buffalo hump can be found in HIV-associated lipodystrophy(26-29) and in MSL(10, 15, 30). It has proposed that the fat in MSL is in the same spectrum as the buffalo hump in HIV-associated lipodystrophy(31). We hypothesize that in fat disorders, especially in AD and MSL, that there can be overlap in the types of abnormal fat present and that more clinical data on these disorders and their overlap is needed as well as laboratory data to distinguish these disorders so that treatments, that might be different for different disorders, can be considered.
Recommendations
1) Stop all alcohol use. Stopping alcohol can stop growth of the MSL fat and perhaps allow it to reduce.
2) Alcohol can be produced by fermentation of food in the gut(32)
3) Pancreatic Enzymes. Try taking pancreatic enzymes on an empty stomach. It is not clear why they work and most traditional physicians like me don’t use them much in practice except if one has pancreatic enzyme deficiency. There is, however, some interesting data on an enzyme supplement called serrapeptidase or serratia peptidase (SP). In a number of studies and conditions, SP appears to have anti-inflammatory, anti-edemic and fibrinolytic (breaks up fibrin) activity when taken by mouth. In pill form, SP is destroyed by acid in the stomach and therefore need to be enteric coated where it is passed to the intestine and absorbed(33). SP has been successfully used to treat symptoms associated with chronic airway disease(34), post-operative edema(35) and inflammation after oral procedures(36, 37) and trauma(35), breast swelling (38), carpal tunnel syndrome in a small trial in India(39), and acute and chronic ear, nose and throat infections(40). SP has never been used to treat AD in a clinical trial. Side effects include rare pneumonitis(41) and blister-like skin eruptions called epidermolysis bullosa(42); with any drug or supplement, rare side effects such as these are possible. To ensure that my patients are getting the product they are ingesting, I like ot write a prescription for Viokase 8 on an empty stomach between meals and at bedtime. Try taking with food if your experience GI upset. If you do buy an enzyme preparation over the counter, to avoid other unnecessary side effects from impurities or poor manufacturing, make sure that the supplement is made by an FDA approved GMP certified facility and is marked as ‘USP’. I checked out Solaray (20,000 international units on an empty stomach) and Ray Sahelian’s brand of products and they are both pharmaceutical grade; you should choose a product that you feel comfortable with.
4) Selenium: Selenium has been shown to decrease edema in tissue. Selenium decreased edema in two placebo controlled trials for post-mastectomy and head and neck radiation(43, 44), it increases the efficacy of physical therapy for lymphedema, it reduces the incidence of erysipelas infections in patients with chronic lymphedema at various sites(43) (and others); it lowers oxygen radical production in part by increasing glutathione peroxidase and thioredoxin reductase; it dcreases glycoprotein adhesion molecules (eg, P-selectin, ICAM-1, VCAM-1, ELAM-1) in a dose-dependent manner(45) which may unclog lymphatic capillaries; it significantly enhanced cellular immunologic reactions improving efficacy of cytotoxic T-lymphocytes and stimulating macrophages degradation of excess tissue proteins(46). The US National Research Council has defined the individual maximum safe dietary intake for selenium as 600 μg daily and the no adverse effect level as 800 μg daily (100 μg selenium in 2 mL of isotonic solution (Biosyn Corporation, Carlsbad, California) = $1600/5 weeks. Anticipate a possible increase in pain or decreased well-being as the toxins come out of the tissue. However, if you don’t feel good taking the selenium, then stop it. You can get sodium selenite solution from Life Extension at 50 mcg per drop (you take 5-10 drops). Many other internet sites also sell the liquid. You can buy 250 mcg tablets from twin labs (try iHerb).
5) Complete Decongestive therapy – This includes decongestive massage, wrapping and garments. A trained therapist in your area can be found here: http://www.vodderschool.com/
and here: http://www.lymphnet.org/resourceGuide/manualDrainage.htm#CA
Learn more here: www.fatdisorders.org
References
1. Brodie, B. (1846) Lectures illustrative of various subjects in pathology and surgery. In pp. 275-276, Longman, London
2. Madelung, O. (1888) Uber den Fetthals. Langenbecks Archiv Klin Chirurg 37, 106
3. Lanois, P., and F, F. B. (1898) L’ade´nolipomatose symmetrique. Bull Soc me´d Hop Paris 1, 289
4. Enzi, G., Biondetti, P. R., Fiore, D., and Mazzoleni, F. (1982) Computed tomography of deep fat masses in multiple symmetrical lipomatosis. Radiology 144, 121-124
5. Enzi, G., Busetto, L., Ceschin, E., Coin, A., Digito, M., and Pigozzo, S. (2002) Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term longitudinal study. Int J Obes Relat Metab Disord 26, 253-261
6. Harsch, I. A., Michaeli, P., Hahn, E. G., Ficker, J. H., and Konturek, P. C. (2003) Launois-Bensaude syndrome in a female with type 2 diabetes. Med Sci Monit 9, CS5-8
7. Nielsen, S., Levine, J., Clay, R., and Jensen, M. D. (2001) Adipose tissue metabolism in benign symmetric lipomatosis. J Clin Endocrinol Metab 86, 2717-2720
8. Kratz, C., Lenard, H. G., Ruzicka, T., and Gartner, J. (2000) Multiple symmetric lipomatosis: an unusual cause of childhood obesity and mental retardation. Eur J Paediatr Neurol 4, 63-67
9. Nounla, J., Rolle, U., Grafe, G., and Kraling, K. (2001) Benign symmetric lipomatosis with myelomeningocele in an adolescent: An uncommon association-case report. J Pediatr Surg 36, E13
10. Busetto, L., Strater, D., Enzi, G., Coin, A., Sergi, G., Inelmen, E. M., and Pigozzo, S. (2003) Differential clinical expression of multiple symmetric lipomatosis in men and women. Int J Obes Relat Metab Disord 27, 1419-1422
11. Donhauser, G., Vieluf, D., Ruzicka, T., and Braun-Falco, O. (1991) [Benign symmetric Launois-Bensaude type III lipomatosis and Bureau-Barriere syndrome]. Hautarzt 42, 311-314
12. Pollock, M., Nicholson, G. I., Nukada, H., Cameron, S., and Frankish, P. (1988) Neuropathy in multiple symmetric lipomatosis. Madelung's disease. Brain 111, 1157-1171
13. Klopstock, T., Naumann, M., Schalke, B., Bischof, F., Seibel, P., Kottlors, M., Eckert, P., Reiners, K., Toyka, K. V., and Reichmann, H. (1994) Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology 44, 862-866
14. Berkovic, S. F., Andermann, F., Shoubridge, E. A., Carpenter, S., Robitaille, Y., Andermann, E., Melmed, C., and Karpati, G. (1991) Mitochondrial dysfunction in multiple symmetrical lipomatosis. Ann Neurol 29, 566-569
15. Klopstock, T., Naumann, M., Seibel, P., Shalke, B., Reiners, K., and Reichmann, H. (1997) Mitochondrial DNA mutations in multiple symmetric lipomatosis. Molecular and Cellular Biochemistry 174, 271-275
16. Chalk, C. H., Mills, K. R., Jacobs, J. M., and Donaghy, M. (1990) Familial multiple symmetric lipomatosis with peripheral neuropathy. Neurology 40, 1246-1250
17. Uglesic, V., Knezevic, P., Milic, M., Jokic, D., and Kosutic, D. (2004) Madelung syndrome (benign lipomatosis): clinical course and treatment. Scand J Plast Reconstr Surg Hand Surg 38, 240-243
18. Fedele, D., Bellavere, F., Bosello, G., Cardone, C., Girardello, L., Ferri, M., and Enzi, G. (1984) Impairment of cardiovascular autonomic reflexes in multiple symmetric lipomatosis. J Auton Nerv Syst 11, 181-188
19. Enzi, G. (1984) Multiple symmetric lipomatosis: an updated clinical report. Medicine (Baltimore) 63, 56-64
20. Nisoli, E., Regianini, L., Briscini, L., Bulbarelli, A., Busetto, L., Coin, A., Enzi, G., and Carruba, M. O. (2002) Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells. J Pathol 198, 378-387
21. Dorigo, P., Prosdocimi, M., Carpenedo, F., Caparrotta, L., Tessari, F., and Enzi, G. (1980) Multiple symmetric lipomatosis. A defect in adrenergic stimulated lipolysis II. Pharmacol Res Commun 12, 625-638
22. Giordano, A., Tonello, C., Bulbarelli, A., Cozzi, V., Cinti, S., Carruba, M. O., and Nisoli, E. (2002) Evidence for a functional nitric oxide synthase system in brown adipocyte nucleus. FEBS Lett 514, 135-140
23. Nisoli, E., Tonello, C., Briscini, L., and Carruba, M. O. (1997) Inducible nitric oxide synthase in rat brown adipocytes: implications for blood flow to brown adipose tissue. Endocrinology 138, 676-682
24. Engeli, S., Janke, J., Gorzelniak, K., Bohnke, J., Ghose, N., Lindschau, C., Luft, F. C., and Sharma, A. M. (2004) Regulation of the nitric oxide system in human adipose tissue. J Lipid Res 45, 1640-1648
25. Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., and Spiegelman, B. M. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124
26. Carr, A., Miller, J., Law, M., and Cooper, D. A. (2000) A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. Aids 14, F25-32
27. Engelson, E. S. (2003) HIV lipodystrophy diagnosis and management. Body composition and metabolic alterations: diagnosis and management. AIDS Read 13, S10-14
28. Lo, J. C., Mulligan, K., Tai, V. W., Algren, H., and Schambelan, M. (1998) "Buffalo hump" in men with HIV-1 infection. Lancet 351, 867-870
29. Heath, K. V., Hogg, R. S., Chan, K. J., Harris, M., Montessori, V., O'Shaughnessy, M. V., and Montanera, J. S. (2001) Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. Aids 15, 231-239
30. Kodish, M. E., Alsever, R. N., and Block, M. B. (1974) Benign symmetric lipomatosis: functional sympathetic denervation of adipose tissue and possible hypertrophy of brown fat. Metabolism 23, 937-945
31. Urso, R., and Gentile, M. (2001) Are 'buffalo hump' syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? Aids 15, 290-291
32. Nair, S., Cope, K., Risby, T. H., and Diehl, A. M. (2001) Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis. Am J Gastroenterol. 96, 1200-1204.
33. Moriya, N., Nakata, M., Nakamura, M., Takaoka, M., Iwasa, S., Kato, K., and Kakinuma, A. (1994) Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem. 20, 101-108.
34. Nakamura, S., Hashimoto, Y., Mikami, M., Yamanaka, E., Soma, T., Hino, M., Azuma, A., and Kudoh, S. (2003) Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease. Respirology. 8, 316-320.
35. Esch, P. M., Gerngross, H., and Fabian, A. (1989) [Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-- a prospective study]. Fortschr Med. 107, 67-68, 71-62.
36. Merten, H. A., Muller, K., Drubel, F., and Halling, F. (1991) [Volumetric verification of edema protection with Serrapeptase after third molar osteotomy]. Dtsch Z Mund Kiefer Gesichtschir. 15, 302-305.
37. Tachibana, M., Mizukoshi, O., Harada, Y., Kawamoto, K., and Nakai, Y. (1984) A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica. 3, 526-530.
38. Kee, W. H., Tan, S. L., Lee, V., and Salmon, Y. M. (1989) The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Singapore Med J. 30, 48-54.
39. Panagariya, A., and Sharma, A. K. (1999) A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J Assoc Physicians India. 47, 1170-1172.
40. Mazzone, A., Catalani, M., Costanzo, M., Drusian, A., Mandoli, A., Russo, S., Guarini, E., and Vesperini, G. (1990) Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 18, 379-388.
41. Sasaki, S., Kawanami, R., Motizuki, Y., Nakahara, Y., Kawamura, T., Tanaka, A., and Watanabe, S. (2000) [Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia]. Nihon Kokyuki Gakkai Zasshi. 38, 540-544.
42. Shimizu, H., Ueda, M., Takai, T., Bito, T., Ichihashi, M., Muramatsu, T., and Shirai, T. (1999) A case of serratiopeptidase-induced subepidermal bullous dermatosis. Br J Dermatol. 141, 1139-1140.
43. Micke, O., Bruns, F., Schäfer, U., Kisters, K., Hesselmann, S., and Willich, N. (2000) Selenium in the treatment of acute and chronic lymphedema. Trace Elements and Electrolytes 17, 206-209
44. Kasseroller, R. G., and Schrauzer, G. N. (2000) Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review. Am J Ther 7, 273-279
45. Horvathova, M., Jahnova, E., and Gazdik, F. (1999) Effect of selenium supplementation in asthmatic subjects on the expression of endothelial cell adhesion molecules in culture. Biol Trace Elem Res 69, 15-26
46. Kiremidjian-Schumacher, L., Roy, M., Glickman, R., Schneider, K., Rothstein, S., Cooper, J., Hochster, H., Kim, M., and Newman, R. (2000) Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res 73, 97-111
Multiple symmetric lipomatosis (MSL) is a rare disease first described by Brodie in 1846(1). Madelung reported data on 33 cases in 1888(2), but the classical description of the disease is attributed to Launois and Bensaude who published a detailed account of 65 cases in 1898(3). The literature on MSL is dominated by research on alcoholic men with a reported incidence of 1/25,000 in the Italian population(4). Nonalcoholics and women are also affected(5-7). Over 270 cases are reported in the literature with an age range varying from 20 to 71 years; two cases have been reported in children(8, 9).
Individuals with MSL have increased fat, usually in a symmetrical distribution either on the neck, upper back (buffalo hump) or interscapular region, on the upper arms or chest, in the mediastinum or thighs, sparing the distal limbs(10). The fat in MSL is thin and watery when removed by needle biopsy unless the individual has undergone numerous liposuction or excision surgeries. When transporting fat in media, the fat will stick to the top of a polystyrene container distinguishing this fat from AD or FML. Because the appearance and location of the lipomatosis can vary, MSL has been divided into three types:(6, 11): TypeI or diffuse lipomatosis of the neck (‘horsecollar lipomata’); Type II or multiple symmetric lipomata of the shoulder girdle, the upper arms, the thorax, the thighs and sometimes the abdomen giving the patients the so called ‘pseudoathletic’ appearance; and Type III or a rare type with preponderance of the lipomatosis in the thigh girth (‘gynecoid type’). Women tend to have Type II and III(10).
Associated disorders include liver disease, hyperlipidemia including elevated high density lipoprotein (HDL) levels (in patients with a history of alcohol use), hypertriglyceridemia, hypothyroidism, diabetes mellitus, and neurological changes(12). MSL is an inherited disorder associated with mitochondrial mutations in a few familial cases,(13, 14) however, Klopstock et al.(15) found mitochondrial mutations in only 2 of 12 patients studied. In addition, Chalk et al. found no mitochondrial pathology or mutations in four siblings with MSL with a pattern favoring autosomal recessive (16).
Morbidity and mortality in MSL is high with sudden non-coronary death accounting for a large percentage of deaths in one series.(5) The neuropathology of MSL is a distal axonal demyelination different from that associated with alcohol intake(12, 16, 17) and impairment of autonomic function has been suggested as a possible cause of sudden death; this impairment seems to be prevalently parasympathetic and not related to a high alcohol intake.(18, 19)
Adipose stem cells from MSL tissue express uncoupling protein (UCP)-1 similar to brown adipose tissue, but fail to increase UCP-1 in response to noradrenaline even though MSL cells express b1-, b2- and b3-adrenergic receptors (AR)(20). In agreement, catecholamines did not induce lipolysis in MSL cells as measured by glycerol release.(21) Because a-AR were not evaluated in this study, these data suggest either a dysregulation in b-AR in the MSL tissue or elevated levels of a-adrenergic receptors.
Adipose tissue express endothelial nitric oxide synthase (NOS)(22) and inducible NOS (iNOS).(23, 24) Noradrenaline did not stimulate expression of iNOS in MSL cells, however, a NO donor inhibited proliferation of these cells and a selective inhibitor of NOS stimulated proliferation. These data suggest a normal response of MSL tissue to NO but defective sympathetic signaling. The sympathetically inducible protein PGC-1, involved in mitochondrial biogenesis in brown adipose tissue (BAT) and other cell types(25), was also not stimulated by noradrenaline in MSL cells as in BAT from rats, supporting a defect in sympathetic nervous system stimulation of MSL tissue(20).
In our survey of 110 individuals with AD, we asked specifically about excess fat on the upper back called a ‘buffalo hump’. Twenty-five (22.7%) individuals had positive responses and 80% of these described the fat as painful. The presence of a buffalo hump can be found in HIV-associated lipodystrophy(26-29) and in MSL(10, 15, 30). It has proposed that the fat in MSL is in the same spectrum as the buffalo hump in HIV-associated lipodystrophy(31). We hypothesize that in fat disorders, especially in AD and MSL, that there can be overlap in the types of abnormal fat present and that more clinical data on these disorders and their overlap is needed as well as laboratory data to distinguish these disorders so that treatments, that might be different for different disorders, can be considered.
Recommendations
1) Stop all alcohol use. Stopping alcohol can stop growth of the MSL fat and perhaps allow it to reduce.
2) Alcohol can be produced by fermentation of food in the gut(32)
3) Pancreatic Enzymes. Try taking pancreatic enzymes on an empty stomach. It is not clear why they work and most traditional physicians like me don’t use them much in practice except if one has pancreatic enzyme deficiency. There is, however, some interesting data on an enzyme supplement called serrapeptidase or serratia peptidase (SP). In a number of studies and conditions, SP appears to have anti-inflammatory, anti-edemic and fibrinolytic (breaks up fibrin) activity when taken by mouth. In pill form, SP is destroyed by acid in the stomach and therefore need to be enteric coated where it is passed to the intestine and absorbed(33). SP has been successfully used to treat symptoms associated with chronic airway disease(34), post-operative edema(35) and inflammation after oral procedures(36, 37) and trauma(35), breast swelling (38), carpal tunnel syndrome in a small trial in India(39), and acute and chronic ear, nose and throat infections(40). SP has never been used to treat AD in a clinical trial. Side effects include rare pneumonitis(41) and blister-like skin eruptions called epidermolysis bullosa(42); with any drug or supplement, rare side effects such as these are possible. To ensure that my patients are getting the product they are ingesting, I like ot write a prescription for Viokase 8 on an empty stomach between meals and at bedtime. Try taking with food if your experience GI upset. If you do buy an enzyme preparation over the counter, to avoid other unnecessary side effects from impurities or poor manufacturing, make sure that the supplement is made by an FDA approved GMP certified facility and is marked as ‘USP’. I checked out Solaray (20,000 international units on an empty stomach) and Ray Sahelian’s brand of products and they are both pharmaceutical grade; you should choose a product that you feel comfortable with.
4) Selenium: Selenium has been shown to decrease edema in tissue. Selenium decreased edema in two placebo controlled trials for post-mastectomy and head and neck radiation(43, 44), it increases the efficacy of physical therapy for lymphedema, it reduces the incidence of erysipelas infections in patients with chronic lymphedema at various sites(43) (and others); it lowers oxygen radical production in part by increasing glutathione peroxidase and thioredoxin reductase; it dcreases glycoprotein adhesion molecules (eg, P-selectin, ICAM-1, VCAM-1, ELAM-1) in a dose-dependent manner(45) which may unclog lymphatic capillaries; it significantly enhanced cellular immunologic reactions improving efficacy of cytotoxic T-lymphocytes and stimulating macrophages degradation of excess tissue proteins(46). The US National Research Council has defined the individual maximum safe dietary intake for selenium as 600 μg daily and the no adverse effect level as 800 μg daily (100 μg selenium in 2 mL of isotonic solution (Biosyn Corporation, Carlsbad, California) = $1600/5 weeks. Anticipate a possible increase in pain or decreased well-being as the toxins come out of the tissue. However, if you don’t feel good taking the selenium, then stop it. You can get sodium selenite solution from Life Extension at 50 mcg per drop (you take 5-10 drops). Many other internet sites also sell the liquid. You can buy 250 mcg tablets from twin labs (try iHerb).
5) Complete Decongestive therapy – This includes decongestive massage, wrapping and garments. A trained therapist in your area can be found here: http://www.vodderschool.com/
and here: http://www.lymphnet.org/resourceGuide/manualDrainage.htm#CA
Learn more here: www.fatdisorders.org
References
1. Brodie, B. (1846) Lectures illustrative of various subjects in pathology and surgery. In pp. 275-276, Longman, London
2. Madelung, O. (1888) Uber den Fetthals. Langenbecks Archiv Klin Chirurg 37, 106
3. Lanois, P., and F, F. B. (1898) L’ade´nolipomatose symmetrique. Bull Soc me´d Hop Paris 1, 289
4. Enzi, G., Biondetti, P. R., Fiore, D., and Mazzoleni, F. (1982) Computed tomography of deep fat masses in multiple symmetrical lipomatosis. Radiology 144, 121-124
5. Enzi, G., Busetto, L., Ceschin, E., Coin, A., Digito, M., and Pigozzo, S. (2002) Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term longitudinal study. Int J Obes Relat Metab Disord 26, 253-261
6. Harsch, I. A., Michaeli, P., Hahn, E. G., Ficker, J. H., and Konturek, P. C. (2003) Launois-Bensaude syndrome in a female with type 2 diabetes. Med Sci Monit 9, CS5-8
7. Nielsen, S., Levine, J., Clay, R., and Jensen, M. D. (2001) Adipose tissue metabolism in benign symmetric lipomatosis. J Clin Endocrinol Metab 86, 2717-2720
8. Kratz, C., Lenard, H. G., Ruzicka, T., and Gartner, J. (2000) Multiple symmetric lipomatosis: an unusual cause of childhood obesity and mental retardation. Eur J Paediatr Neurol 4, 63-67
9. Nounla, J., Rolle, U., Grafe, G., and Kraling, K. (2001) Benign symmetric lipomatosis with myelomeningocele in an adolescent: An uncommon association-case report. J Pediatr Surg 36, E13
10. Busetto, L., Strater, D., Enzi, G., Coin, A., Sergi, G., Inelmen, E. M., and Pigozzo, S. (2003) Differential clinical expression of multiple symmetric lipomatosis in men and women. Int J Obes Relat Metab Disord 27, 1419-1422
11. Donhauser, G., Vieluf, D., Ruzicka, T., and Braun-Falco, O. (1991) [Benign symmetric Launois-Bensaude type III lipomatosis and Bureau-Barriere syndrome]. Hautarzt 42, 311-314
12. Pollock, M., Nicholson, G. I., Nukada, H., Cameron, S., and Frankish, P. (1988) Neuropathy in multiple symmetric lipomatosis. Madelung's disease. Brain 111, 1157-1171
13. Klopstock, T., Naumann, M., Schalke, B., Bischof, F., Seibel, P., Kottlors, M., Eckert, P., Reiners, K., Toyka, K. V., and Reichmann, H. (1994) Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology 44, 862-866
14. Berkovic, S. F., Andermann, F., Shoubridge, E. A., Carpenter, S., Robitaille, Y., Andermann, E., Melmed, C., and Karpati, G. (1991) Mitochondrial dysfunction in multiple symmetrical lipomatosis. Ann Neurol 29, 566-569
15. Klopstock, T., Naumann, M., Seibel, P., Shalke, B., Reiners, K., and Reichmann, H. (1997) Mitochondrial DNA mutations in multiple symmetric lipomatosis. Molecular and Cellular Biochemistry 174, 271-275
16. Chalk, C. H., Mills, K. R., Jacobs, J. M., and Donaghy, M. (1990) Familial multiple symmetric lipomatosis with peripheral neuropathy. Neurology 40, 1246-1250
17. Uglesic, V., Knezevic, P., Milic, M., Jokic, D., and Kosutic, D. (2004) Madelung syndrome (benign lipomatosis): clinical course and treatment. Scand J Plast Reconstr Surg Hand Surg 38, 240-243
18. Fedele, D., Bellavere, F., Bosello, G., Cardone, C., Girardello, L., Ferri, M., and Enzi, G. (1984) Impairment of cardiovascular autonomic reflexes in multiple symmetric lipomatosis. J Auton Nerv Syst 11, 181-188
19. Enzi, G. (1984) Multiple symmetric lipomatosis: an updated clinical report. Medicine (Baltimore) 63, 56-64
20. Nisoli, E., Regianini, L., Briscini, L., Bulbarelli, A., Busetto, L., Coin, A., Enzi, G., and Carruba, M. O. (2002) Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells. J Pathol 198, 378-387
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