Factors determining the optimal body site and method for obtaining punch biopsies of human skin as a tissue in which to assess pharmacodynamic and pharmacokinetic endpoints in drug development studies.

There are potential advantages to detecting pharmacodynamic (PD) and pharmacokinetic (PK) endpoints in a tissue-based compartment such as the skin during the development of molecularly targeted drugs. We explored regional differences between inner arm, inner thigh, lower back and buttocks in 12 healthy male Caucasian volunteers in the tolerability of skin biopsy procedures; the Ki67 proliferation index; the frequency of detecting hair follicles and sweat glands; and the percentage of melanocytes. We also explored the amounts of tissue and protein obtained, and two separate methods of splitting biopsies for processing in mutually exclusive media. Biopsies from all body sites were well tolerated. The subjective ranking order was inner arm > buttocks = back > thigh. There were no statistically significant differences in the Ki67 labelling index (P > 0.05). The frequency of detecting sweat glands was the same in all body sites, but the frequency of detecting hair follicles was higher in back and buttock, compared to arm and thigh. The percentage of melanocytes was significantly lower in the buttocks compared to the back and thigh (P < 0.05), but not compared to the arm (P = 0.07). A 4-mm punch biopsy yielded a mean of 16.8 mg of tissue (range: 9-28 mg) and 160 microg of protein (range: 80-270 microg). In vivo sample splitting, by following a 2-mm punch with a 4-mm overpunch, had a shorter time from devascularisation to immersion into processing medium than ex vivo dissection of a 4-mm sample, which may be of importance to the assessment of labile endpoints. We conclude that multiple punch biopsies of the skin are feasible, with the buttocks representing the studied body site with the optimal balance between tolerability, hair follicle density and melanocyte density for obtaining tissue in which to assess PD and PK endpoints during drug development studies.

Pelvic congestion syndrome: early clinical results after transcatheter ovarian vein embolization.

PURPOSE: This case series describes the early radiographic and clinical results of attempted transcatheter ovarian vein (OV) embolization in 11 women with symptoms that were suggestive of the pelvic congestion syndrome (PCS). METHODS: Eleven women (mean age, 33.1 years) who were multiparous were referred for lower extremity or vulvar varicosities (n = 8) or for tubo-ovarian varicosities (n = 3). After a clinical diagnosis of PCS was established, the women underwent ovarian (n = 5) or ovarian and iliac vein (n = 6) venography. Enlarged or incompetent OVs were embolized with 0.035-inch stainless steel coils or with 0.018-inch platinum microcoils and absorbable gelatin sponge. Incompetent tributaries to hypogastric veins were embolized as well (n = 1). Symptoms before embolization and after embolization were recorded with a standard questionnaire, and the post-embolization symptoms were expressed as individual and overall percent relief. RESULTS: Nine of the 11 women underwent embolization. Embolization of both OVs (n = 4), of the left OV alone (n = 4), or of a left obturator vein that communicated with vulvar varices (n = 1) was performed. Eight of the 9 women (88.9%) had more than 80% immediate relief. Overall and individual symptom relief varied from 40% to 100% at the mean 13.4-month follow-up. One woman with variant anatomy and one woman with evidence of prior left OV thrombosis were not treated. There were no major complications. Two women had a mild to moderate return of the symptoms at 6 and 22 months. CONCLUSIONS: Transcatheter embolization provides excellent initial and variable midterm relief in women with typical PCS symptoms and with OV or OV and internal iliac (hypogastric) tributary vein incompetence. This interventional technique may replace or complement the traditional surgical approaches to this rarely recognized and poorly understood disease.

Doppler analysis of hemodialysis grafts: resistive index as a predictor of stenosis.

A series of six hemodialysis vascular access patients was evaluated with duplex Doppler sonography and angiography to identify Doppler sonographic parameters that are predictors of venous outflow stenosis. This preliminary series indicates that no venous outflow stenosis was present angiographically when the resistive index gradient across the venous anastomosis is less than or equal to zero and a significant venous outflow stenosis (50 to 100%) was present when the resistive index gradient is 0.15 or greater (P = 0.002, r = 0.963). Doppler acquisition of resistive index gradients across regions of venous outflow is a promising, noninvasive means of rapid radiologic evaluation of hemodialysis graft patients, especially when the need for angiography is equivocal.