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REDfly: a Regulatory Element Database for Drosophila.

Bioinformatics studies of transcriptional regulation in the metazoa are significantly hindered by the absence of readily available data on large numbers of transcriptional cis-regulatory modules (CRMs). Even the richly annotated Drosophila melanogaster genome lacks extensive CRM information. We therefore present here a database of Drosophila CRMs curated from the literature complete with both DNA sequence and a searchable description of the gene expression pattern regulated by each CRM. This resource should greatly facilitate the development of computational approaches to CRM discovery as well as bioinformatics analyses of regulatory sequence properties and evolution.

Animals↗

Protective effect of cloricromene, a coumarine derivative, in hypovolemic hemorrhagic shock in the rat.

Hypovolemic hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min until mean arterial pressure (MAP) fell to 30 mm Hg. Survival rate, MAP, plasma myocardial depressant factor (MDF) activity and plasma levels of both TxB2 and 6-keto PGF1 alpha were then evaluated. Cloricromene (0.5, 1, and 2 mg/kg) or an equal volume of vehicle (0.9% NaCl solution) were injected intravenously 5 min after the end of the bleeding. Hemorrhagic shocked rats showed enhanced plasma levels of MDF, TxB2 and 6-keto PGF1 alpha. All vehicle-treated rats died within 25 min. Cloricromene (1 and 2 mg/kg) given curatively significantly increased survival rate and blunted the rise in plasma MDF and TxB2. Moreover, cloricromene reversed the severe hypotension and the ST-segment elevation occurring during hemorrhagic shock. The data suggest that cloricromene exerts beneficial effects in experimental hypovolemic shock, probably reversing myocardial failure.

6-Ketoprostaglandin F1 alpha↗

An economic evaluation of two ototopical treatments for acute otitis media in tympanostomy tube patients.

OBJECTIVE: The goal of this research was to determine the cost-effectiveness of ciprofloxacin 0.3%/dexamethasone 0.1% (CD) otic suspension versus ofloxacin 0.3% otic solution (OFX) for treatment of acute otitis media in tympanostomy tube patients. METHODS: A decision-analytic model was used to emulate the ototopical treatment of acute otitis media in patients with tympanostomy tubes. The economic outcome was the cost per otorrhea-free day (OFD) achieved per episode of care. Three tiers of antimicrobial therapy were modeled, with each successive tier representing the retreatment of clinical failures from the preceding tier. First-tier therapy compared CD and OFX using outcome measures obtained from a randomized clinical trial (n = 599). Second-tier therapy modeled the use of amoxicillin/clavulanate (ACA) using outcome measures obtained from a physician survey and medical literature. Third-tier therapy was modeled as pathogen-specific and curative. It could follow one of three pathways: 1) intramuscular ceftriaxone; 2) oral fluconazole; or 3) hospitalization for intravenous antibiotics. Third-tier outcomes were based on a physician survey. Cost data were obtained from standard references and presented from a payer perspective. RESULTS: The expected therapeutic costs were 249.40 dollars for the CD pathway and 265.44 dollars for the OFX pathway. The estimated number of OFDs per episode of care was 25.88 for the CD pathway and 23.86 for the OFX pathway. The cost-effectiveness ratios for CD and OFX therapies were 9.64 dollars and 11.13 dollars per OFD, respectively. CONCLUSION: CD is both more effective and less costly than OFX for the treatment of acute otitis media in patients with tympanostomy tubes.

Acute Disease↗

Taking stock of gene therapy for cystic fibrosis.

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy.

Animals↗

The effects of concrete objective information and relaxation on maintaining usual activity during radiation therapy.

PURPOSE/OBJECTIVES: To examine the effects of concrete objective information (COI) and relaxation instruction (RI) on patients undergoing radiation therapy, as well as the contribution of symptom uncertainty and body awareness to the intervention effects. DESIGN: Three-group randomized trial. Assignment was stratified by cancer site. Data collectors were blinded to group assignments. SETTING: University medical center radiation therapy department serving both urban and rural communities in the southeastern United States. SAMPLE: 76 adults having radiation with curative intent for gynecologic, head and neck, or lung cancer. Most were Caucasian and had in situ to stage II disease. Mean age was 55 years. METHODS: COI and RI were delivered by tape recordings. Outcome measures were indicators of usual activities and emotions at treatment week 3 and two and four weeks post-treatment. MAIN RESEARCH VARIABLES: Intervention group; social, household, and recreational activities; anxiety, depression, and anger; body awareness; and symptom uncertainty. FINDINGS: Participants receiving either intervention reported more social activity during treatment. Those given RI who were high in body awareness reported more household activity during treatment. No effects were found regarding emotion. Symptom uncertainty partially explained COI effects. CONCLUSIONS: The findings provide additional support for the effectiveness of COI in helping patients to maintain more of their usual activities during radiation therapy. Instruction in progressive muscle relaxation also may help in maintaining activities. IMPLICATIONS FOR NURSING: COI helps patients to cope with treatment by reducing their uncertainty about symptoms. RI effects may vary by activity type and awareness of usual body sensations.

Activities of Daily Living↗

Nursing assessment of sexual function following permanent prostate brachytherapy for patients with early-stage prostate cancer.

Assessment of sexual function following potentially curative local treatment for carcinoma of the prostate gland has resulted in wide ranges of potency preservation rates, which may be because of differences in the evaluated patient populations, mode of data collection, and length of patient follow-up. Quality-of-life data are most reliable when obtained by patient-administered and validated quality-of-life instruments. In the Schiffler Cancer Center's prostate brachytherapy unit, healthcare professionals utilize the specific erectile questions of the International Index of Erectile Function to ascertain pre- and post-treatment erectile function. Documentation of sexual function following all local treatments, including prostate brachytherapy, may help to clarify the etiology of treatment-induced erectile dysfunction (ED), improve treatment for ED, and, ultimately, improve quality-of-life outcomes. Fortunately, the majority of patients with brachytherapy-induced ED respond favorably to sildenafil citrate.

Adenocarcinoma↗

Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.

PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.

Biomarkers↗

Screening for chronic impairments using medical interns in rural Haryana, India.

BACKGROUND: With the increase in life expectancy, prevalence of impairments and disabilities are expected to increase in India. However, there have been very few studies to estimate the magnitude of the problem in rural India. This is essential, if appropriate rehabilitation services are to be planned in the country. METHODS: The study was done in the rural field practice area of the All India Institute of Medical Sciences at Ballabgarh, Haryana. The survey was conducted by successive batches of interns posted at Ballabgarh as a part of their compulsory rotating internship programme. The diagnostic criteria were based on history and simple clinical examination done at the domiciliary level. RESULTS: A total population of 25,509 in twelve villages were screened. The total impairment rate was 5.4% with no significant men/women difference. The prevalence of physical impairment was 4.7 per 1000 population. The prevalence of corneal opacity in children below 15 years of age was 4.7 per 1000. Prevalence of cataract was almost 35% in the population over 60 years of age and 15% in the population between 45 to 60 years. Auditory impairment was 19.6 per 1000 as ascertained by history. Three-fourths of this was conductive deafness and was found mainly in people above 60 years of age. CONCLUSION: Utilizing the rural field practice areas of medical colleges for collection of data on issues of national health importance would not only strengthen the health system in the country but also improve medical education. There is a need for a comprehensive preventive, promotive, curative and rehabilitative approach to disabilities in India.

Adolescent↗

Adenocarcinoma of the gastric cardia: treatment via a left thoracoabdominal approach.

We examined the outcome of adenocarcinomas of the gastric cardia treated by total or proximal gastrectomy, lower esophagectomy, and D2 lymphadenectomy via a left thoracoabdominal approach. We compare these results with those of other methods as well as review the literature. During a 10-year period (1991-2000) 180 patients with primary gastric cancer were admitted to our department. Thirty-six of the patients had adenocarcinoma of the cardia. Twenty-four patients underwent total gastrectomy, D2 lymphadenectomy, and esophagectomy, and four others underwent proximal gastrectomy and esophagectomy with esophagogastric anastomosis via a left thoracoabdominal approach. These latter 28 patients compose our study group. We had no operative mortality, the morbidity varied, and the quality of life and the loss of body weight ranged within satisfactory levels, but the survival rate was rather poor. The median survival time was 19 +/- 1.2 months. Survival was significantly longer in patients with less than 40 per cent positive resected lymph nodes (P = 0.035). From the resulting data and our experience we believe that the left thoracoabdominal approach gives excellent exposure for radical resection of cancer of the gastric cardia and should be the procedure of choice for curative resection of such tumors. This approach combined with total gastrectomy and D2 lymphadenectomy can be performed with an acceptably low mortality rate; it provides good palliation but not encouraging survival rates. Although it is less radical proximal gastrectomy gives the same results and a better quality of life but may be performed only in the early stages of the disease.

Adenocarcinoma↗

[Radiotherapy of the maxillary sinus cancers].

Between 1983 and 1988, 23 patients with cancer of maxillary sinus were treated with either postoperative radiotherapy or radiation alone at the Radiation Oncology Department, Veterans General Hospital-Taichung. There were 20 males and 3 females, 38 to 80 years of age with median age of 60 years. Nineteen were of epidermoid type and 4 were of other histologic types. There were 11 cases of T3 and 12 cases of T4. Only 1 case had neck lymph node metastasis. All patients had bony destruction shown in sinus X-ray films before treatment. Four patients received radiation alone because they refused or were unsuitable for operation. Nineteen patients received postoperative radiotherapy. For radiation alone 70-80 Gy in 7-8 weeks was given in open fields or wedge filters by cobalt-60 gamma radiation. For postoperative radiotherapy, all patients were treated with wedge filters with 50-80 Gy in 5-8 weeks by cobalt-60 radiation also. The minimum followup period was 29 months. All patients treated with radiation alone expired within 2 years with median survival time of 9 months. The 5-year survival rate of postoperative therapy was 40.3% with median survival time of 26.8 months. The overall 5-year survival rate was 33.4% with median survival time of 17 months. There was no significant difference in 5-year survival rate between T3 (34.1%) and T4 (33.3%). The data indicated no survival difference in different types of operation. The therapy of radiation alone was not advocated and the total dose of postoperative radiotherapy should be over 60 Gy for curative purpose.

Adult↗

[Chemotherapy for advanced and recurrent cancer patients--the effect of combination chemotherapy using cisplatin, peplomycin, mitomycin C, adriamycin, and 5-fluorouracil].

According to the data obtained from the fundamental investigations using flow cytometry we designed the schedule of combination chemotherapy for solid cancer patients and we tried this therapy on 25 patients with non-curative, unresectable and recurrent cancers: 9 gastric, 5 colo-rectal, 3 esophageal, 3 pancreatic, 2 gall bladder, 2 lung and 1 breast cancer. The treatment was performed every 3 or 4 weeks as follows: CDDP 70 mg/m2 (d.i.), PEP 4 mg/m2 (i.v.) and MMC 4 mg/m2 (i.v.) on day 1, ADM 15 mg/m2 (i.v.) on day 4, and 5-Fu 250 mg/body (d.i.) every day. Among 22 patients evaluated completely, 1 complete response, 9 partial responses, 11 no changes, 1 progressive disease were obtained. The overall response rate was 45%. From the comparison of survival curves, survival rate was significantly better in patients responded to this therapy than in patients who did not respond to it (p less than 0.05). As for side effects, myelosuppression occurred in 19 patients (86%), increase of BUN and/or creatinine were observed in 3 patients (14%), increase of GOT and/or GPT were seen in 10 patients (45%), gastrointestinal symptoms and alopecia were observed in almost all patients, but all of these toxicity were transient and did not impede the continuous treatment.

Adult↗

De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Northern Region Haematology Group.

A 4-year prospective study of de novo acute myeloid leukaemia in patients aged 56 years and over was undertaken in the Northern Region of England (population 3.09 million). The study was conducted to assess the incidence and outcome of treatment in all elderly patients diagnosed between January 1, 1988 and December 31, 1991. Two hundred cases de novo AML were confirmed, giving an incidence of 6.05/10(5) per annum (age specific population) (95% Cl, 5.2-6.9). Acute promyelocytic leukaemia was rare. Erythroleukaemia, monocytic leukaemia and AML with trilineage myelodysplasia were more common than in younger patients. Karyotypic abnormalities classically associated with response to therapy were present in only six of 91 patients where cytogenetic data was available. Treatment was at the discretion of the physician in charge: if given, specific treatment was recorded and clinical outcome assessed. Only 84 (42%) of patients received treatment with curative intent. Forty-four of 84 achieved a complete remission, usually of brief duration. A normal karyotype in leukaemic cells was associated with a survival advantage in this group (p < 0.05). Actuarial overall survival at 4 years for the entire group was 2.5%. Even with aggressive treatment, the outcome is poor. The pattern of disease and its lack of response to conventional treatment would support the hypothesis that AML in the elderly may differ biologically from that observed in younger patients. Karyotyping appears to predict those patients likely to benefit from intensive therapy and decisions about management in otherwise fit patients should, if possible, be delayed until a result is obtained. Every effort should be made to give such patients optimal treatment. However, most patients are unsuitable for aggressive treatment and, since long-term survival is rare, cure should not be offered as an inducement to accept such treatment and improving quality of life outside hospital should be the aim of treatment in this group.

Acute Disease↗

Potential contribution of therapy to cancer mortality reduction.

Reductions in cancer mortality may come about for a number of reasons, including improvements in treatment. The impact will vary from cancer to cancer. For some, expert curative surgery is crucial, whereas for others, the use of appropriate chemotherapy is a key factor. Examples of the latter, in which there are already discernible reductions in national cancer mortality data resulting from chemotherapy, include testicular cancer and Hodgkin's disease. For more common diseases, such as ovarian cancer, reductions also are being seen. For others, such as breast and colorectal cancer, the current more widespread use of adjuvant chemotherapy may lead to overall mortality reduction in the future. It should be recognized that chemotherapy should be given only by those experienced in its use, and that this facility should form part of a larger provision for health care in relation to cancer, ranging from public education to population screening and from better oncology training for clinicians to greater encouragement to participation in clinical trials. New drug development is clearly a priority, but further advances can be made in many countries already using available forms of chemotherapy if treatment facilities are organized appropriately.

Adult↗

A prospective analysis of staging laparoscopy in patients with primary and secondary hepatobiliary malignancies.

Laparoscopy and laparoscopic ultrasound are used widely in cancer staging and are perceived to prevent unnecessary open exploration in many patients. The aim of this study was to analyze the impact of staging laparoscopy in improving resectability in patients with primary and secondary hepatobiliary malignancies. Over a 10-month period (November 1, 1997 to August 31, 1998), 186 patients with primary and secondary hepatobiliary cancers were submitted to operation for potentially curative resection. One hundred four patients staged laparoscopically (LAP) before laparotomy were compared prospectively to 82 patients undergoing exploration without laparoscopy (NO LAP). Assignment to each group was not random but was based on surgeon practice. Demographic data, diagnoses, the extent of preoperative evaluation, and the percentage of patients resected were similar in the two groups. Laparoscopy identified 26 (67%) of 39 patients with unresectable disease. In the NO LAP group, 28 patients (34%) had unresectable disease discovered at laparotomy. In patients with unresectable disease and submitted to biopsy only, the operating times were similar in the two groups (LAP 83 +/- 22 minutes vs. NO LAP 91 +/- 33 minutes; P = 0.4). However, laparoscopic staging significantly reduced the length of hospital stay (LAP 2.2 +/- 2 days vs. NO LAP 8.5 +/- 8.6 days; P = 0.006). Likewise, total hospital charges, normalized to 100 in the NO LAP patients, were significantly lower in the LAP group (LAP 54 +/- 42 vs. NO LAP 100 +/- 84; P = 0.02). Staging laparoscopy identified the majority of patients with unresectable hepatobiliary malignancies, significantly improved resectability, and reduced the number of days in the hospital and the total charges. The yield of laparoscopy was greatest for detecting peritoneal metastases (9 of 10), additional hepatic tumors (10 of 12), and unsuspected advanced cirrhosis (5 of 5) but often failed to identify nonresectability because of lymph node metastases, vascular involvement, or extensive biliary involvement. Eighty-three percent of patients subjected to laparotomy after laparoscopy underwent a potentially curative resection compared to 66% of those who were not staged laparoscopically.

Biliary Tract Neoplasms↗

Diamond-Blackfan anemia.

Diamond Blackfan anemia is a rare congenital hypoplastic anemia that usually presents early in infancy. Congenital anomalies, in particular of the head and upper limbs, are present in about 25% of reported patients. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. Recent genetic studies have led to the identification of mutations in the ribosomal protein RPS19 in approximately 25% of sporadic and familial cases, a second gene on chromosome 8p, and evidence for an additional locus (or loci). The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Patients who do not respond to treatment are usually transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.

Combined Modality Therapy↗

[Analytical data on the aquifer strata in the city of Iaşi].

In this paper are presented the results of the analytical study of some sources of water from Botanic Garden, Iaşi, Romania. This sources contained a distinguished water, hypo and hypertonic, which can be used as curative magnesiene water.

Mineral Waters↗

The National Prostate Cancer Register in Sweden 1998-2002: trends in incidence, treatment and survival.

OBJECTIVES: To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. MATERIAL AND METHODS: Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35,223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. RESULTS: Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged < 70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA > 100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8-10) had a markedly reduced relative 5-year survival rate. CONCLUSIONS: It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Age Distribution↗

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression.

OBJECTIVES: To investigate the efficacy and tolerability of bicalutamide (Casodex) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with localized or locally advanced (T1b-T4, any nodal status, M0) prostate cancer. METHODS: This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial in Europe, South Africa, Australia, and Mexico and is part of the Casodex Early Prostate Cancer program. RESULTS: A total of 3603 men were randomized to receive bicalutamide (n = 1798) or placebo (n = 1805). The patient demographics were well balanced between the two groups. Prior therapy of curative intent had been given to 64% of the patients (prostatectomy [44%], radiotherapy [18%], and prostatectomy and radiotherapy [2%]) and 36% had been monitored with watchful waiting. After a median follow-up of 2.6 years and a median exposure to the study drug of 2.2 years, a significant 43% reduction in the risk of objective progression was observed for the bicalutamide group compared with the placebo group (hazard ratio 0.57, 95% confidence interval 0.48 to 0.69, P << 0.0001). The time to prostate-specific antigen doubling was significantly delayed for the bicalutamide group compared with the placebo group (hazard ratio 0.37, 95% confidence interval 0.32 to 0.43, P << 0.001). The survival data were immature, with 7.2% overall mortality. The most frequently reported adverse events with bicalutamide were gynecomastia alone (17.4%), breast pain alone (17.6%), and gynecomastia with breast pain (47.5%). CONCLUSIONS: Bicalutamide 150 mg daily as immediate therapy, alone or as adjuvant to treatment of curative intent, significantly reduced the risk of disease progression in patients with localized or locally advanced prostate cancer. Longer follow-up is underway to assess any benefit in overall survival.

Adult↗