Second-look laparotomy for stage III epithelial ovarian cancer: rationale and current issues

During the past two decades, the initial treatment of an advanced ovarian malignancy has been generally uniform: it begins with an exploratory laparotomy surgically to remove as much tumor as possible (1) and to stage the cancer (2). For the 70% of patients classified as stages III and IV, surgery is then followed by combination chemotherapy. Although opinions differ as to the optimal regimen, the standard involves a platinum-based program (3), recently also including paclitaxel (4). A second-look laparotomy is often performed in all patients who achieve a clinical complete remission, that is the inability to detect disease by physical examination and non-invasive laboratory tests. This surgical procedure is able to detect clinical disease not apparent on computerized axial tomography (CT scan), ultrasound, magnetic resonance imaging (MRI), serum CA-125 levels or physical examination (5-7). Major questions, however, have arisen around the need for such a procedure, and whether one can justify it in terms of an improved outcome or merely as an assessment of prognosis (8-14). We shall review: (i) the technique; (ii) the rationale; (iii) the results that have been reported from its routine application; and (iv) controversial issues, particularly as they relate to the evolution of therapeutic strategies.     

Transient expression of beta-galactosidase in differentiating sporozoites of Eimeria tenella

A cocktail of seven Listeria monocytogenes isolates of food, human and environmental origin was used to assess the antilisterial activity of the bacteriocins nisin and ALTA 2341 in combination with various atmospheres: air, 100% N2, 40% CO2:60% N2, or 100% CO2. Buffered tryptone soya broth (pH 6.0) was used as the growth medium and incubation was at 4 degrees C (21 days) or 12 degrees C (7 days), or when temperature fluctuated between these values for defined periods. It was observed that atmosphere alone influenced the growth rate of L. monocytogenes, with 100% CO2 exerting the greatest inhibition. A 5 log population increase was observed in all atmospheres after 7 days at 12 degrees C. At 4 degrees C a 4-5 log population increase was observed in air, 100% N2 and 40% CO2:60% N2 within 21 days. Growth was prevented by 100% CO2. In the presence of nisin (400 IU/ml), an increase in the lag phase was observed before growth (5 log population increase after 7 days) in all atmospheres at 12 degrees C. This effect was enhanced at 4 degrees C where a maximum 2 log population increase was observed in all atmospheres except 100% CO2, in which growth was prevented. Increasing the concentration of nisin to 1250 IU/ml prevented L. monocytogenes growth in all atmosphere combinations at 4 and 12 degrees C. Two concentrations of ALTA 2341 were also tested. In the presence of 0.1% ALTA 2341 and at 12 degrees C, a 3-5 log population increase was observed in all atmospheres with the exception of 100% CO2, which prevented L. monocytogenes growth. At 4 degrees C, growth was observed in the combination of 0.1% ALTA 2341 and 100% N2 only (3 log population increase). Use of a higher concentration of ALTA 2341 (1.0%) resulted in a population decrease below the detection level within 24 h in all atmosphere/temperature combinations. Re-growth occurred in the presence of 1.0% ALTA 2341 in all atmospheres at 12 degrees C, and in combination with air or 100% N2 at 4 C. When the effectiveness of either nisin or ALTA 2341 and atmosphere was tested against L. monocytogenes as temperature fluctuated for periods between 4 and 12 degrees C, only the combination of 100% CO2 and 1.0% ALTA 2341 prevented growth. Cells surviving exposure to nisin or ALTA 2341 were recovered from 28 of the 32 combinations tested that contained bacteriocin. Nisin survivors remained sensitive to the bacteriocin. ALTA 2341 survivors had become resistant to the bacteriocin.     

Catnip and the alteration of human consciousness

Uncertainty exists regarding the ability of catnip (Nepeta cataria) to affect human consciousness. We report a case of a toddler exhibiting central nervous system depression after consuming a large quantity of catnip. His obtundation was not attributable to another cause. We review the published literature describing the alleged psychoactive capabilities of catnip and present our case as further information for use in this ongoing controversy.     

Results of efficacy study with diclofenac/orphenadrine infusions in patients with musculoskeletal diseases and functional disorders

During a post-marketing surveillance study, 641 patients (age range 18 to 86 years) with painful rheumatic diseases, mostly of vertebral etiology, were given ready-for-use infusions containing a combination of the non-steroid antiphlogistic agent diclofenac (75 mg) and the muscle relaxing agent orphenadrine (30 mg) parenterally for 7 days. The goal of the study was to investigate efficacy, tolerability, and acceptance of this intravenous therapy in wide use in physicians' practices. At the end of treatment, the global evaluation resulted in a score of 1.6 on a scale of 1 (very good) to 4 (insufficient). The tolerability score was 1.3 and the acceptability score was 1.5. Only 20 patients (3.1%) had adverse effects, most of which were of gastrointestinal nature. The medication proved appropriate for use in the treatment of painful spine syndromes, inflammatory osteoarthritis, painful osteoporosis, post-operative conditions, and extra-articular rheumatism and could represent a first step towards multi-factorial therapeutic management of these diseases.     

Complex shape changes in isolated rat osteoclasts: involvement of protein kinase C in the response to calcitonin

Recent developments in the functional and neural bases of several aspects of memory are described including long term cortical memory storage, the transition from immediate to permanent memory mediated by medial temporal structures, working memory, memory retrieval, and implicit memory. These are linked to current data on the nature of anterograde and retrograde amnesia in the degenerative diseases, and also to issues in the clinical diagnosis of memory impairments. Understanding the bases of memory can inform the diagnosis of memory impairments in degenerative diseases, and the patterns of impairment seen in the degenerative diseases can help contribute to knowledge of the mechanisms of normal memory.     

Correlation between hyperproliferation and suprabasal integrin expression in human epidermis reconstituted in culture

In normal epidermis integrin expression is largely confined to the basal layer. However, during wound healing and in psoriatic lesions suprabasal expression is observed. Although the potential importance of suprabasal integrin expression in the pathogenesis of psoriasis has been established, the cause of suprabasal expression is unknown. We now describe changes in integrin expression that occur with time when normal human keratinocytes are grown on two types of dermal equivalent, de-epidermized dermis and collagen gels containing fibroblasts. We show that suprabasal integrin expression is correlated with suprabasal expression of the EGF receptor, but not with expression of keratin 10 or keratin 16. By quantitating the proportion of basal keratinocytes expressing the proliferation marker Ki-67 we could show that suprabasal integrin expression is correlated with high proliferative activity within the basal layer. Taken together with our earlier work, these results suggest that suprabasal integrin expression is linked to hyperproliferation and not to abnormal terminal differentiation or to inflammation; they also establish dermal equivalent cultures as useful experimental models with which to manipulate keratinocyte integrin expression.     

Consequences of hyperhomocyst(e)inemia on vascular function in atherosclerotic monkeys

Moderate elevation of plasma homocyst(e)ine is associated with increased risk for atherosclerotic vascular disease. In a previous study, we observed impaired vascular function in nonatherosclerotic monkeys with moderate hyperhomocyst(e)inemia. In this study, we tested the hypothesis that dietary intervention to lower plasma homocyst(e)ine corrects vascular dysfunction in atherosclerotic monkeys. Cynomolgus monkeys were fed an atherogenic diet that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. After 17 months, the atherogenic diet was supplemented with B vitamins (5 mg folic acid, 400 micrograms vitamin B-12, and 20 mg vitamin B-6 daily) for 6 months. Total plasma homocyst(e)ine decreased from 12.8 +/- 2.8 to 3.5 +/- 0.3 mumol/L (n = 9; mean +/- SE; P < .01) after vitamins were added to the diet, but plasma cholesterol remained elevated (522 +/- 63 versus 514 +/- 41 mg/dL; P > .05). In response to intra-arterial infusion of collagen, blood flow to the leg decreased by 30 +/- 3% and 38 +/- 5%, respectively, before and after vitamin supplementation (P > .05). In vivo responses of resistance vessels to endothelium-dependent vasodilators (acetylcholine or ADP) were impaired at baseline and did not improve after vitamin supplementation. In carotid artery studied ex vivo, relaxation to low doses of acetylcholine improved after vitamin supplementation, but maximal relaxation remained impaired. Ex vivo thrombomodulin anticoagulant activity was threefold higher in monkeys fed the atherogenic diet (with or without B vitamins) than in normal monkeys (P < .05). We conclude that normalization of plasma homocyst(e)ine is insufficient to restore normal vascular function in atherosclerotic monkeys with persistent hypercholesterolemia and that atherosclerosis, with or without hyperhomocyst(e)inemia, is associated with elevated thrombomodulin activity.     

Effect of 13-cis-retinoic acid and alpha-interferon on transforming growth factor beta1 in patients with rising prostate-specific antigen

The objective of this study was to test the hypothesis that 13-cis-retinoic acid (CRA) and alpha-interferon (IFN-alpha) have antitumor activity in patients with early recurrence of prostate cancer measured by rising prostate-specific antigen (PSA) after local therapy, and that this activity is associated with the increase of plasma transforming growth factor beta1 (TGF-beta1). Thirty patients with a PSA > 7 ng/ml that increased >0.4 ng/ml/month after initial radiation therapy or a PSA > 2.0 ng/ml after prostatectomy were treated with 1 mg/kg/day of CRA and 3 million units of IFN-alpha administered three times per week. Patients were followed clinically with serum measurements of PSA and assessment of toxicity. Biological activity of CRA and IFN-alpha was assessed by the measurement of plasma TGF-beta1. Twenty-six percent of patients had a partial (50% decrease maintained for 1 month) or minimal (<50% decrease maintained for 1 month) biochemical response of PSA, with a median decrease of 23% (11-55%) at 3 months. Plasma TGF-beta1 levels increased with CRA and IFN-alpha therapy and correlated with a decrease in PSA; patients with a decrease in PSA had a 151% increase in TGF-beta1 compared to 27% in patients without a decrease in PSA (P = 0.04). CRA and IFN-alpha can produce transient reduction or stabilization of PSA. The measurement of plasma TGF-beta1 at 1 month of therapy correlates with changes in PSA and may represent a useful marker for the biological effect of these agents; further analysis in larger numbers of patients and methods to optimize these effects should be explored.