Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects.

Introduction: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer.

Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation.

Purpose: Lometrexol [(6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate] is the prototype folate antimetabolite that targets the de novo purine synthesis pathway. Early phase I trials were confounded by cumulative myelosuppression that prevented repetitive administration. Subsequent preclinical and clinical studies suggested that coadministration of folic acid might favorably modulate lometrexol toxicity without eliminating potential antitumor activity.

Reducing the risk of malpractice claims.

Many physicians will be sued for malpractice at some time during their careers. Risk of litigation can be reduced by adopting practices that include keeping thorough medical records, educating office personnel, and fostering good patient-physician relationships. The last is important because patients who view their physicians as caring tend not to sue even if an adverse outcome occurs.

pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation.

Background: The onset of differentiation-specific gene expression in skeletal muscle is coupled to permanent withdrawal from the cell cycle. The retinoblastoma tumor-suppressor protein (pRb) is a critical regulator of this process, required for both cell-cycle arrest in G0 phase and high-level expression of late muscle-differentiation markers. Although the cell-cycle defects that are seen in pRb-deficient myocytes can be explained by the well-described function of pRb as a negative regulator of the transition from G1 to S phase, it remains unclear how pRb positively affects late muscle-gene expression.

Concurrent paclitaxel and radiation therapy for breast cancer.

Few studies have evaluated the role of concurrent chemoradiation therapy in the management of locally advanced breast cancer. The availability of radiosensitizing chemotherapeutic agents that are effective in breast cancer and the encouraging results achieved by concurrent chemoradiation in other malignancies have prompted us to investigate this approach. Paclitaxel is a promising agent for use with concurrent radiotherapy because of its single-agent efficacy profile and its radiosensitizing effects.

Seckel-like syndrome in three siblings.

Seckel syndrome has been described as the prototype of the primordial bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60 cases have been reported. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic, endocrine, and central nervous systems.

Rat mesangial cells express two unique isoforms of laminin which modulate mesangial cell phenotype.

Rat mesangial cells express two unique isoforms of laminin which can be modulated by culture medium composition. To define further the nature of laminin expressed by cultured rat mesangial cells, synthesis of individual laminin chains, as well as their trimeric association, was examined. Based on data from Northern analysis of mRNA expression, immunoblots, immunofluorescence staining and radioimmunoprecipitation of biosynthetically labeled proteins, mesangial cells express laminin beta1, beta2, and gamma1 chains.

Rabbit urethral regeneration using small intestinal submucosa onlay grafts.

Objectives: To determine if small intestinal submucosa (SIS) can evoke urethral regeneration.

Methods: Twenty male white New Zealand rabbits were assigned to one of three experimental groups. Group 1 (n = 4) underwent simple urethrotomy and closure.

The detection of changes in mammographic densities.

We previously reported reductions in mammographic densities in women participating in a trial of a gonadotropin-releasing hormone agonist (GnRHA)-based regimen for breast cancer prevention. In our previous report, we compared (by simultaneous evaluation) three basic elements of mammographic densities. The purpose of the present study was to evaluate whether a standard (expert) method of measuring mammographic densities would detect such changes in densities and whether a novel nonexpert computer-based threshold method could do so.

Preoperative 5-fluorouracil and radiation therapy for locally advanced breast cancer.

Background: Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

Purpose/objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer.

Diabetes induces changes in glomerular development and laminin-beta 2 (s-laminin) expression.

Offspring of diabetic mothers have developmental renal abnormalities; thus, we investigated the effects of the diabetic milieu on kidney development. Four groups of host rats, including insulin-deficient and insulin-treated streptozotocin-induced diabetic rats, normal controls, and insulin-treated nondiabetic rats, were prepared. After 38 days, rats received ocular implants of E14 fetal rat kidneys.

Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.

Purpose: To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer.

Patients And Methods: Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans.

Insulin-like growth factor I (IGF-I) induces unique effects in the cytoskeleton of cultured rat glomerular mesangial cells.

Resident glomerular mesangial cells (MCs) have complex cytoskeletal organizations that maintain functional and structural integrity. The ability of cells to replicate, coordinate movement, change shape, and interact with contiguous cells or extracellular matrix depends on cytoskeletal organization. MCs synthesize insulin-like growth factor (IGF-I), express IGF-I receptors, and respond to IGF-I with increased proliferation.

Erosion rate of the double cuff AMS800 artificial urinary sphincter: long-term followup.

Purpose: We reviewed the erosion rate of the double cuff artificial urinary sphincter.

Materials And Methods: Charts of 95 patients were evaluated for erosions and underlying etiology.

Results: Ten patients had erosion of the cuffs, for an erosion rate of 10.

Phase I and pharmacokinetic study of oral UFT, a combination of the 5-fluorouracil prodrug tegafur and uracil.

UFT is an oral preparation combining the 5-fluorouracil (FU) prodrug tegafur (FT) and uracil (U) in a 1:4 ratio, which is commercially available in Japan for the treatment of breast and gastrointestinal cancers. We sought to determine the tolerance of daily oral UFT and to relate this tolerance to the pharmacokinetics of FT and/or the derived FU, while exploring the possibility of circadian FU kinetics contributing to the results. A 28-day schedule followed by 2 weeks rest was began at the initial level of 300 mg/m2/day administered either at 8 a.

Roller-blades: should they carry a government health warning?

Rollerblading is increasingly popular in the UK. Over 12 weeks, we treated 29 patients of whom 34 per cent required operative intervention. There was a wide range of injuries, those of the radius being most common, and some (e.

Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist.

The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription factors are expressed in the myotome of developing somites and cooperatively activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome. Ectopically expressed mouse Twist (Mtwist) was shown to inhibit myogenesis by blocking DNA binding by MyoD, by titrating E proteins, and by inhibiting trans-activation by MEF2.

Long-term experience with the double-cuff AMS 800 artificial urinary sphincter.

Objectives: To assess the efficacy and safety of the double-cuff artificial urinary sphincter over a long-term period.

Methods: Ninety-five patients charts were reviewed from December 1986 to November 1995. Data on the degree of urinary incontinence and complications were compiled and tabulated.

Sonohysterographic imaging of the endometrial cavity.

Vaginal ultrasound is the most effective method of imaging the contents of the true pelvis in the female. Saline influsion sonohysterography (SIS) is a simple refinement of the standard vaginal sonographic exam. Here, we briefly describe and demonstrate our use of this latter technique.