Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis.

BACKGROUND. The antibody Ki-67 binds to nuclei in all cell cycle phases except GO and can be used to measure growth fraction. Because proliferative activity has been linked to prognosis in neoplasia, the authors analyzed 100 cases of colorectal carcinoma, each with 3 or more years of follow-up, using Ki-67 immunostaining. METHODS. The Ki-67-positive nuclear area and total nuclear area of carcinoma cells in 20 microscopic fields were measured by computed morphometry. A Ki-67 score (percent positive nuclear area x 100) was calculated. The following characteristics also were recorded for each case: patient age and sex, tumor site and size, modified Dukes' stage, spread beyond bowel wall, lymph node status, tumor grade, histologic type, extramural venous spread, tumor growth pattern, fibrosis, lymphocytic infiltration, and mitotic rate. RESULTS. Ki-67 scores ranged from 1 to 90 (mean, 34.6). Ki-67 scores were higher in Stage A disease (versus Stage B, C, and D disease) but were not associated with survival. Survival curves differed by stage, lymph node metastases, infiltrative growth pattern, lymphocytic infiltration, fibrosis, extramural venous spread, and tumor grade in a univariate analysis. The infiltrative growth pattern (P = 0.04) and lymphocytic infiltration (P = 0.003) were features associated independently with survival after adjusting for modified Dukes' stage. Furthermore, the lack of a significant lymphocytic infiltrate was associated with a death rate 3.4 times greater than that occurring in patients with Stage B disease with a significant infiltrate. CONCLUSIONS. The authors conclude that proliferative activity in colorectal carcinoma as measured by Ki-67 immunostaining was not associated with prognosis.     

Septic separation of the symphysis pubis

Summary Symphysial osteomyelitis has been distinguished from osteitis pubis because of the more serious nature of the disease. We report a case in which there was a pelvic separation similar to that seen after trauma or pregnancy. The previously undescribed complications of bladder perforation and pelvic instability are also noted. There was no predisposing cause in this case, in contrast to the 40 previously reported. The causative organism was staphylococcus aureus, but pseudomonas aeruginosa and escherichia coli have also been found in other cases.

---

Résume L'ostéomyélite de la symphyse pubienne a pu être distinguée de l'ostéite pubienne en raison de sa plus grande gravité. Nous en rapportons un cas dans lequel existait une disjonction symphysaire semblable à celles que l'on observe après traumatisme ou grossesse. On a également noté des complications jamais décrites, à savoir une perforation vésicale et une instabilité pelvienne. Il n'y avait pas de cause prédisposante dans ce cas, contrairement aux 40 observations précédemment rapportées dans la littérature. La bactérie causale était un staphylocoque doré, mais le pyocyanique et le colibacille ont également été retrouvés dans d'autres cas.

     

Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.     

Effect of illuminated nifedipine, a potent antioxidant, on intestinal and vascular smooth muscles.

1. The effects of nifedipine (Nif) and its illuminated nitroso product nitrosopine (NTP) were investigated on lipid peroxidation, KCl elevated smooth muscle tension, and ionic currents of single smooth muscle cells. 2. Illumination of Nif at 400-700 nm within 24-48 h changed it completely to a potent antioxidant, NTP. 3. Nif relaxed the KCl-induced contractions of guinea-pig taenia caeci and rat aorta and reduced the amplitude of the evoked inward Ca2+ current of taenia caeci cells in a concentration-dependent manner. NTP (up to 100 microM) was ineffective in this respect. Pretreatment by NTP (10 microM) did not affect the actions of Nif. 4. The evidence suggests that NTP, generated by day-light illumination from Nif, exerts antioxidant activity but is devoid of voltage-dependent Ca2+ channel (VDC) blocking property and does not interfere with the action of Nif on the smooth muscle cell membrane VDC.     

Development of a reconstructed human skin model for angiogenesis

We have previously shown that reconstructed human skin engineered from autologous keratinocytes, fibroblasts, and sterilized donor allodermis stimulates angiogenesis within 5-7 days when placed on well-vascularized wound beds in nude mice. When this reconstructed skin was used clinically in more demanding wound beds, some grafts were lost, possibly due to delayed vascularization. As this reconstructed skin lacks any endothelial cells, our aim in this study was to develop an angiogenic reconstructed skin model in which to explore strategies to improve angiogenesis both in vitro and in vivo. We report that culture of small-vessel human dermal microvascular endothelial cells (HuDMECs) was achieved using magnetic beads coated with an antibody to platelet cell adhesion molecule as a means of purifying the culture. Keratinocytes, fibroblasts, and HuDMECs could be cultured from the same skin biopsy. Initial studies culturing HuDMECs and other sources of endothelial cells with the tissue-engineered skin showed that these cells were capable of slowly entering the dermis under standard culture conditions in vitro. In conclusion, this provides us with a model in which to explore strategies for improving angiogenesis in vitro and also establishes the culture methodologies for the production of reconstructed skin containing autologous keratinocytes, fibroblasts, and endothelial cells.