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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Pseudo Biologist who wrote (22242)	6/15/1998 6:18:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

PB, Although PI's help KS, I did notice that the small study did not find any complete remissions. LGND's study has indicated that Panretin is effective against refractory patients and is independent of responses to PI's. The small study suggested an indirect effect (bolstering of the immune system) for PI related improvements and LGND's data suggested that Panretin works by an independent mechanism. Thus, AIDS patients who are in better health and have a partial remission in KS may in fact be an expanding market because they live longer and their KS is improved, but still present.

To: Pseudo Biologist who wrote (22242)	6/16/1998 8:30:00 AM
From: Henry Niman	Respond to of 32384

Speaking of protease inhibitors, effects on metabolism are showing up with increasing frequencies in AIDS patients: paradise-web.com The fat deposits and increased cholesterol level could generate a new target population for rexinoids and TZDs.

To: Pseudo Biologist who wrote (22242)	6/16/1998 8:35:00 AM
From: Henry Niman	Respond to of 32384

Here's more on altered metabolism associated with PI's: AIDS 1998 May 7;12(7):F51-F58 A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA HIV Medicine Unit and Centre for Immunology, St Vincent's Hospital, Sydney, Australia. [Medline record in process] OBJECTIVE: To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. DESIGN: Cross-sectional study. SETTING: Outpatient clinic of a university teaching hospital. PATIENTS: HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47). INTERVENTIONS AND MAIN OUTCOME MEASURES: Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. RESULTS: HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. CONCLUSION: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon. PMID: 9619798, UI: 98281097

To: Pseudo Biologist who wrote (22242)	6/16/1998 8:37:00 AM
From: Henry Niman	Respond to of 32384

Here's another recent abstract: AIDS 1998 Apr 16;12(6):F37-F39 Indinavir-associated lipodystrophy. Viraben R, Aquilina C Service de Dermatologie, Toulouse, France. BACKGROUND: Lipodystrophies are rare cutaneous disorders characterized by the symmetrical loss of subcutaneous fat from the body surface. The cause of lipodystrophy is not known, but a possible genetic predisposition is likely and either overt diabetes mellitus or insulin resistance are often associated. DESIGN AND METHODS: Case study. PATIENTS: Eight patients who developed either partial or generalized lipodystrophy after protease inhibitor therapy. RESULTS: In all eight patients lipodystrophy occurred after 2-12 months of starting indinavir and was not preceded by weight loss or inflammatory skin disease. Short-term follow-up after withdrawal of therapy showed no change in the patients' appearance. One patient developed glycosuria as lipodystrophy became manifest. In three cases glucose tolerance test was performed revealing a high level of insulin between the first and third hour of loading. CONCLUSIONS: In our view, lipodystrophy is an unwanted side-effect of protease inhibitor therapy causing noticeable disfigurement. PMID: 9583592, UI: 98242894

To: Pseudo Biologist who wrote (22242)	6/16/1998 9:09:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here are some anecdotal reports on protease pouches / buffalo humps and PIs: paradise-web.com