Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer

Background. Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. Methods. We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. Results. The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0–19, median 5 days) and IBR groups (range 0–40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p=0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. Conclusions. Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.     

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A – 30mg/m² i.v. weekly; Arm B – leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 15, q 28days; Arm C – mitoxantrone 12mg/m² i.v. only day 1+leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 13, q 28days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3–4 toxicities.Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.     

Morphometric study of collagen maturation in chick compact bone

An ultrastructural-morphometric study was carried out on the process of osteoid maturation in growing surfaces of parallel-fibered chick bone. The aim was to investigate the distribution, size and amount of collagen fibrils (CFs), as well as the proteoglycan (PG) content, throughout the osteoid seam and in the adjacent bone. The results show that the organic components secreted by osteoblasts undergo complete maturation inside the osteoid seam only. Proceeding from the secreting plasma membrane of osteoblasts (osteoidogenic surface) towards the mineralizing surface, we found that CFs gradually increase in diameter but not in number per surface unit. As a consequence, the proportion of osteoid seam occupied by CF increases too, at the expense of the interfibrillar substance. PG content also decreases inversely in this direction. In the adjacent bone, CF size and density do not change significantly with respect to the mature osteoid close to the mineralizing surface.     

Disappearance of bovine insulin from plasma in diabetic and normal subjects

Disappearance curves for radioiodinated and immunoreactive bovine insulins were determined and analyzed in 30 subjects (5 normal volunteers and 25 diabetic patients). Simultaneous determinations were made of blood glucose and of insulin binding by insulin antibodies. There was significant negative association between the disappearance of bovine insulin from plasma and the insulin-binding level of circulating insulin antibodies. The presence of diabetes, the clinical character of the diabetes (whether stable or unstable), and the presence of chronic diabetic complications, of themselves, had no apparent significant influence that could be separated from the effect of circulating levels of insulin-binding antibodies on the disappearance of bovine insulin from plasma.     

Novel cationic copolymers of a polyasparthylhydrazide: synthesis and characterization

,β-poly(asparthylhydrazide) (PAHy), a water soluble synthetic polymer, was functionalized by using EDCI chemistry with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) obtaining carboxypropyltrimethyl ammonium copolymers (PAHy-CPTA). Three PAHy-CPTA copolymers at increasing derivatization degrees (38%, 48%, 58%) were chosen for subsequent investigations. The capability of these copolymers to bind, neutralize, and protect DNA against degradation by DNase II was evalued by gel retardation assay and DNA degradation test at pH 5.5. Zeta potential measurements show that all studied polymers are able to neutralize the anionic charge of DNA at polymer/DNA weight ratio in the range of 0.8/1-5/1. Polyplex dimensional distribution analyses in bistilled water, saline solution NaCl 0.9%, and HEPES pH 7 show that polyplex size is strongly affected by both presence and type of electrolyte and with time incubation.     

Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs

The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg(-1)) decreased bronchial resistance in basal conditions and significantly (P < 0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg(-1), i.v.) and VIII (0.3 mg kg(-1), i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders.     

Variability and growth in spending for outpatient specialty pharmaceuticals

Specialty pharmaceuticals are a unique group of drug agents used to treat complex clinical conditions. Many specialty pharmaceuticals are biological in nature and administered through injection or infusion. Tracking spending on these pharmaceuticals is complex, because these products may be processed as either medical or pharmacy claims. This benchmarking study of ten Blue Cross Blue Shield plans, representing almost eighteen million covered lives, documents large expenditures on select specialty pharmaceutical categories and much variation in spending across plans, age groups, and time. Our results underscore the need for insurers to scrutinize trends in specialty pharmaceutical spending and identify appropriate management strategies.