Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

Dysphagia aortica

Three patients with dysphagia caused by compression of the distal esophagus by a tortuous nonaneurysmal atherosclerotic aorta are described. All three patients were elderly women; systemic hypertension and cardiomegaly were present in two patients. Barium studies of the esophagus showed displacement and compression of the distal esophagus by the thoracic aorta. Debilitating dysphagia was treated surgically in one patient. The other two patients had milder symptoms and were managed conservatively. Esophageal manometry in these three patients showed superimposed pulsations and elevated intraluminal pressure just proximal to the lower esophageal sphincter. To evaluate the significance of these manometric findings and their correlation with clinical symptoms, we reviewed manometric tracings in 47 normal subjects. Ten of these subjects had an elevation of baseline intraluminal esophageal pressure as a result of superimposed vascular pulsations. We conclude that (1) compression of the distal esophagus by a tortuous atherosclerotic aorta in the appropriate setting can lead to clinically significant dysphagia and (2) a manometric finding of vascular compression of the esophagus does not necessarily correlate symptomatic dysphagia.     

Improvement in the Appearance of Wrinkles with Topical Transforming Growth Factor β1 and l-Ascorbic Acid

BACKGROUND AND OBJECTIVE: Facial rhytides are a common cosmetic concern. Surgical treatment effects dramatic improvement; however, the associated risk and cost may be prohibitive. Recent focus is on developing topical products containing biologically active ingredients for at-home therapy. Our study examines the effects of a topical cream containing transforming growth factor-beta(1) (TGF-beta(1)), l-ascorbic acid, and Cimicifuga racemosa extract (CRS) (Topix Pharmaceuticals, North Amityville, NY, USA). MATERIALS AND METHODS: In the first arm of the study, 12 subjects were randomized to apply CRS to the left or right side of their face and a cream containing l-ascorbic acid and C. racemosa in silicone base (vitamin C [Vit C]) to the contralateral side twice daily for 3 months. In the second arm of the study, 20 subjects were randomized to apply CRS to the left or right side of their face and Tissue Nutrient Solution Recovery Complex (TNS) (SkinMedica, Carlsbad, CA, USA), a product containing a variety of growth factors including VEGF, PDGF-A, G-CSF, HGF, IL-6, IL-8, and TGF-beta(1) (Nouricel-MD) without l-ascorbic acid, C. racemosa extract, or silicone base, to the contralateral side of their face twice daily for 3 months. Digital photographs were scored by study-blinded physicians, and self-assessments were completed by all subjects at baseline and at the conclusion of the protocol. RESULTS: CRS and TNS were well tolerated, and all subjects completed the 3-month protocol for the CRS versus Vit C arm of the study. Physicians rated success in facial wrinkling scores on the CRS-treated side of the face for 27 of 31 subjects. Responders showed, on average, 21.7% improvement in physician-rated wrinkle scores. The mean improvement in the group of 31 patients as a whole was 12%. Eighteen of 31 subjects reported a noticeable improvement on their CRS-treated side. Both CRS and TNS demonstrate significant success between baseline and 3-month scores, and both growth factor products are superior to Vit C. Patients preferred CRS over TNS. CONCLUSION: CRS is effective in minimizing the appearance of facial rhytides. The success of the CRS product is largely attributable to the incorporation of TGF-beta(1).