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PubMed1991

Mapping sequenced E.coli genes by computer: software, strategies and examples.

Methods are presented for organizing and integrating DNA sequence data, restriction maps, and genetic maps for the same organism but from a variety of sources (databases, publications, personal communications). Proper software tools are essential for successful organization of such diverse data into an ordered, cohesive body of information, and a suite of novel software to support this endeavor is described. Though these tools automate much of the task, a variety of strategies is needed to cope with recalcitrant cases. We describe such strategies and illustrate their application with numerous examples. These strategies have allowed us to order, analyze, and display over one megabase of E. coli DNA sequence information. The integration task often exposes inconsistencies in the available data, perhaps caused by strain polymorphisms or human oversight, necessitating the application of sound biological judgment. The examples illustrate both the level of expertise required of the database curator and the knowledge gained as apparent inconsistencies are resolved. The software and mapping methods are applicable to the study of any genome for which a high resolution restriction map is available. They were developed to support a weakly coordinated sequencing effort involving many laboratories, but would also be useful for highly orchestrated sequencing projects.

Base Sequence↗
PubMed1984

Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection.

In the United States, there are an estimated 5000 to 6000 new patients annually who might be candidates for major hepatic resection to treat their recurrent colon cancer. Since 1971, the program reported here has evaluated various factors that might influence the curative potential of such an approach. Sixty-five patients had a major hepatic resection from March 1971 through May 1982. Using a stepwise proportional hazard analysis, all data that had been stored in CLINFO (a data analysis system by Bolt, Beranek and Newman; Boston, MA) were evaluated for the effect of multiple variables on the survival of patients with resected hepatic metastases. Twenty-seven had a right hepatic lobectomy; 14 had extended right hepatectomy with one having the caudate lobe also removed; ten had left lobectomy, nine had left lateral segmentectomy; and five had a major hepatic resection with three-dimensional wedge excision of a metastatic deposit in the contralateral lobe. The 30-day operative mortality rate was 7% (4/58) for patients undergoing the standard major hepatic resection. It was 14% for seven patients in whom the isolation-hypothermic perfusion technique was used early in the series. In ten patients, wedge excision only was required to remove the tumor. Stage I disease is defined as tumor confined to the resected portion of the liver without invasion of major intrahepatic vessels or bile ducts. Stage II disease is regional spread and Stage III disease is metastasis to lymph nodes or extraregional sites. The 3-year survival estimate was 66% for the 37 patients with Stage I disease. The 3-year survival estimate for 13 patients with Stage II disease was 58%. Five of the nine patients with Stage III disease are presently alive from 3 to 23 months; one of the other four died at 35 months of disease. The stage of liver disease was the most significant variable in this survival analysis (p = 0.02); Dukes' classification of colorectal primary was significant at p less than 0.05. Those factors found not to be significant determinants of survival were: number of metastatic hepatic deposits, site of colon primary, age, sex, preoperative liver function tests, and CEA.

Adult↗
PubMed1995

Developing an information system to support the pursuit of decentralization. The perspective of Cearà State in Brazil.

Discusses the national health information system in Brazil which, until very recently, consisted of two main structures of health services with a dichotomy between curative and preventive health care acting in a vertical manner. The autonomy of health authorities and specialized structures created numerous independent health information systems with different methods of data collection. Although the issues of decentralization and a unified health system had been agreed on in 1963, they had not been implemented until the new health policy reform was lunched in 1988. The reform was based on the strengthening of primary health care at national level and accelerating decentralization of health systems. However, in spite of strong political will the new health managers at local level are lacking essential information, data and instruments that only a decentralized health management information system can provide. Based on a study conducted in the Cearà State of the north east of Brazil, explores how the present health information system can support the process of decentralization.

Brazil↗
PubMed1986

Some international comparisons of mortality amenable to medical intervention.

A series of outcome indicators was proposed for assessing the curative aspects of health care using several diseases for which evidence suggested that death was largely avoidable provided that appropriate medical treatment could be given in time. International data were examined for those causes for which data were readily available. Time trends in mortality were compared for each of these conditions for six countries that had experienced appreciable growth in health services during 1950-80. Mortality from the heterogeneous "avoidable" causes had declined faster than mortality from all other causes in each of the six countries. Despite problems of diagnosis, reporting, and classification of diseases that may have existed among countries, making international comparisons of absolute mortality difficult, the trends of declining mortality were similar, lending credibility to the use of these causes of mortality as indices of health care within countries. Changes within countries may also have been attributable to changes in social, environmental, genetic, and diagnostic factors, which were not examined. Nevertheless, the consistency in mortality trends for this group of "amenable" diseases suggested that improvements in medical care were a factor in their rapid decline.

Adolescent↗
PubMed2005

Effect of lung cancer surgery on quality of life.

BACKGROUND: Health related quality of life (HRQOL) after surgery is important, although very limited data are available on the QOL after lung cancer surgery. METHODS: The effect of surgery on HRQOL was assessed in a prospective study of 110 patients undergoing potentially curative lung cancer surgery at Papworth Hospital, 30% of whom had borderline lung function as judged by forced expiratory volume in 1 second. All patients completed the EORTC QLQ-C30 and LC13 lung cancer module before surgery and again at 1, 3 and 6 months postoperatively. RESULTS: On average, patients had high levels of functioning and low levels of symptoms. Global QOL had deteriorated significantly 1 month after surgery (p = 0.001) but had returned to preoperative levels by 3 months (p = 0.93). Symptoms had worsened significantly at 1 month after surgery but had returned to baseline levels by 6 months. Low values on the preoperative HRQOL scales were not significantly associated with poor surgical outcome. However, patients with low preoperative HRQOL functioning scales and high preoperative symptom scores were more likely to have poor postoperative (6 months) QOL. The only lung function measurement to show a marginally statistically significant association with quality of life at 6 months after surgery was percentage predicted carbon monoxide transfer factor (Tlco). CONCLUSION: Although surgery had short term negative effects on quality of life, by 6 months HRQOL had returned to preoperative values. Patients with low HRQOL functioning scales, high preoperative symptom scores, and preoperative percentage predicted Tlco may be associated with worse postoperative HRQOL.

Adult↗
PubMed2006

Protein ranking by semi-supervised network propagation.

BACKGROUND: Biologists regularly search DNA or protein databases for sequences that share an evolutionary or functional relationship with a given query sequence. Traditional search methods, such as BLAST and PSI-BLAST, focus on detecting statistically significant pairwise sequence alignments and often miss more subtle sequence similarity. Recent work in the machine learning community has shown that exploiting the global structure of the network defined by these pairwise similarities can help detect more remote relationships than a purely local measure. METHODS: We review RankProp, a ranking algorithm that exploits the global network structure of similarity relationships among proteins in a database by performing a diffusion operation on a protein similarity network with weighted edges. The original RankProp algorithm is unsupervised. Here, we describe a semi-supervised version of the algorithm that uses labeled examples. Three possible ways of incorporating label information are considered: (i) as a validation set for model selection, (ii) to learn a new network, by choosing which transfer function to use for a given query, and (iii) to estimate edge weights, which measure the probability of inferring structural similarity. RESULTS: Benchmarked on a human-curated database of protein structures, the original RankProp algorithm provides significant improvement over local network search algorithms such as PSI-BLAST. Furthermore, we show here that labeled data can be used to learn a network without any need for estimating parameters of the transfer function, and that diffusion on this learned network produces better results than the original RankProp algorithm with a fixed network. CONCLUSION: In order to gain maximal information from a network, labeled and unlabeled data should be used to extract both local and global structure.

Algorithms↗
PubMed2002

An evaluation of bicalutamide in the treatment of prostate cancer.

Prostate cancer is a major health problem in men, causing significant morbidity and mortality. Although traditionally considered a disease of old age, improved diagnostic techniques have resulted in earlier diagnosis and many men are now treated while still physically and sexually active. Current therapies for prostate cancer, which include medical or surgical castration, have a significant impact on many aspects of quality of life. The non-steroidal antiandrogen bicalutamide (Casodex, AstraZeneca) has a favourable tolerability profile with demonstrated efficacy in several stages of prostate cancer and represents an alternative therapeutic strategy to castration. Mature survival data from men with previously untreated, locally-advanced disease reveal that bicalutamide monotherapy provides survival benefits that do not differ significantly from castration, while offering important advantages with respect to the maintenance of physical capacity and sexual interest. Recent data from a prospective randomised trial, the largest prostate cancer treatment study ever conducted, demonstrate that immediate therapy with bicalutamide (alone or as an adjuvant to therapy of curative intent) significantly reduces the risk of objective disease progression in patients with localised or locally-advanced prostate cancer. Antiandrogens are also used in combination with castration (combined androgen blockade) for advanced disease. Another large, randomised trial demonstrated that combined androgen blockade with bicalutamide is associated with a similar survival outcome to combined androgen blockade with flutamide and is better tolerated. The evidence reviewed demonstrates that bicalutamide currently has a favourable risk:benefit ratio in several stages of prostate cancer. The role of bicalutamide will be further defined by ongoing studies.

Anilides↗
PubMed2005

Los alamos hepatitis C immunology database.

The Los Alamos Hepatitis C Virus (HCV) Sequence Database (http://hcv.lanl.gov or http://hcv-db.org) was officially launched in September 2003. The sister HCV Immunology Database was made public in September 2004. The HCV Immunology Database is based on the Human Immunodeficiency Virus (HIV) Immunology Database. The HCV Immunology Database contains a curated inventory of immunological epitopes in HCV and their interaction with the immune system, with associated retrieval and analysis tools. This article describes in detail the types of data and services that the new database offers, the tools provided and the database framework. The data and some of the HCV database tools are available for download for non-commercial use.

Journal Article↗
PubMed1999

The chemotherapy of head and neck cancer.

Chemotherapy in head and neck cancer can be given in metastatic disease at presentation, in locally far advanced disease not amendable for curative treatment with surgery and/or radiotherapy, in the neo-adjuvant setting, in recurrent disease after previous surgery and radiotherapy and either concurrent or alternating with radiotherapy. Most data are gathered in the recurrent and locally far advanced disease setting. Combination therapy (with agents such as cisplatinum, 5-FU and methotrexate) have shown some improvements in response rate, however no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck has been observed. In the neo-adjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New compounds and approaches are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease are the taxanes. With monotherapy docetaxel, response rates of 23%-42% are seen, and, when used in combination with cisplatinum and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neo-adjuvant therapy with cisplatinum and 5-FU is now underway.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

[Nursing consultation: analysis of actions in programs for arterial hypertension, in Fortaleza].

The nurses' performance in a hypertension and diabetes programs has been important, once its approach is not only directed to illness, but also to the patient as a whole. Therefore, the nursing consultation is a unique moment of this approach. This is a descriptive study aiming at searching the activities performed in the nursing consultations that are performed within Hypertension Programs in the city of Fortaleza, State of Ceará, Brazil. The data were gathered from March to May 1999, with 14 nurses, who work in these services. Data were analyzed according to Bardin's content analysis as well as the categorical analysis. The results showed that the nursing consultation is still based on the traditional curative medical model. The activities performed by nurses are restricted to anamnesis, brief physical examination and diet orientations, medications, walks and use of infusions. In the consultations, individual care prevails, without considering family and group approaches.

Brazil↗
PubMed2004

Diagnosis of isolated dextrocardia using angiocardiography or surgery.

BACKGROUND: Isolated dextrocardia is a rare phenomenon and usually associated with multiple cardiac anomalies. This study was to evaluate the accuracy of diagnosis of isolated dextrocardia by using angiocardiography and to compare it with the results of surgery. METHODS: The clinical data of 27 cases of congenital isolated dextrocardia were collected to understand the diagnostic approaches to the major cardiac anomalies. All cases underwent angiocardiography followed by palliative or curative surgery. The diagnosis was compared by angiocardiography relying on segmental analysis with the pathological features observed in surgery. RESULTS: The results of angiocardiography of 22 patients were the same as the pathological features observed during surgery, including one case with congenital left ventricular diverticulum was inadvertently omitted in angiocardiograhy. There were significantly dissimilar diagnoses between angiocardiograhy and post-operation in 5 patients, including anatomical corrected transposition of great arteries misinterpreted as corrected transposition of the great arteries in 1, complete transposition of great arteries misinterpreted as corrected transposition of the great arteries in 1, single ventricle misinterpreted as double-outlet right ventricle in 1, and anatomical double-outlet left ventricle misinterpreted as corrected transposition of the great arteries in 2. Misdiagnostic rate of angiocardiograhy was almost 20%. CONCLUSIONS: Angiocardiography is of great significance in the diagnosis and classification of isolated dextrocardia. However, because of the intricacy of cardiac anomalies of isolated dextrocardia, atrial angiography and double oblique projection are needed to improve the accuracy of diagnosis to support surgical treatments.

Adolescent↗
PubMed1991

Introduction: the clinical challenge.

In summary, ondansetron has proved to be a highly effective anti-emetric and is superior to metoclopramide in the treatment of acute emesis. The results in delayed emesis are less consistent, with superiority demonstrated in both non-cisplatin and radiotherapy studies, but rather equivocal results in cisplatin studies to date. Ondansetron exhibits minimal toxicity with no reported acute dystonic effects. This clearly is an obvious benefit - particularly in young patients. In three of the trials there was a crossover design which generated patient preference data (Table 5). Nausea and vomiting are very distressing but not life-threatening side effects; they are side effects to be tolerated by patients embarking on potentially curative chemotherapy. In the final analysis, patient preferences for a specific anti-emetic may well be one of the most important parameters by which a new anti-emetic should be judged. Since the London symposium, ondansetron has been introduced in the UK and New Zealand (Trademark ZOFRAN) and France (Trademark ZOPHREN). The objective of a satellite symposium to the 15th International Cancer Congress, Hamburg, held in August 1990, was to review new studies involving ondansetron and evaluate the clinical performance in a database of more than 5,500 cancer patients, including a significant paediatric contribution.

Antiemetics↗
PubMed1991

[Usefulness of folinic acid in cytopenia induced by antiparasitic drugs in AIDS patients].

The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Obstruction of the extrahepatic bile ducts by tumor debris and/or clots in primary cancer of the liver. Diagnostic and therapeutic problems. Apropos of 9 personal cases and review of the literature].

The onset of jaundice in patients with primary liver cancer is sometimes caused by intra ductal biliary system tumor casts, free floating debris or hemobilia. The diagnosis of this complication is now possible by E.R.C.P. or P.T.C. We report 9 cases of unrecognized primary liver tumor revealed by intra biliary system migration of tumor casts or free floating debris. In three patients the diagnosis was operative, but for the last six cases the E.R.C.P. data in addition with U.S., C.A.T. Scan and/or hepatic angiography were helpful in determining the nature of the hepatic and biliary changes, the operability (size, location, extent). A curative surgery was not indicated in our 8 operated patients: liver resection and biliary decompression. With the palliative procedures, bilio enteric by pass (2 cases) T tube (1 case) trans hepatic uni or bilateral tubes. The survey was not longer than 11 months. Three patients died in post operative course. Only 56 patients among 117 observations of the literature have been operated: 10 liver resections including the main hepatic junction in two cases were performed with one hospital death, two patients were alive over 2 years with recurrence and three patients were disease free with a follow up less than one year. The operative mortality with palliative procedures was 34.4%; the one-two years survival was 23%; the two longest survivors lived 41 and 61 months.

Adenoma, Bile Duct↗
PubMed1984

[Pharmacokinetics and pharmacological aspects of interferons].

It has been well established that interferon (IFN) has a variety of biological activities. It was originally discovered as an antiviral agent, but later its antitumor action was clearly demonstrated in many laboratories. Systemic treatment with IFN has been used in various experimental animals in order to determine its prophylactic or curative potential against virus infection and cancer. Clinical application of IFN is now making progress and increasingly being performed in human patients. Therefore, it would be valuable if data on the tissue distribution, decay rate and metabolism of the injected material were available. However, until now researchers have been appeared to be reluctant to extensively explore this area. The toxicology of IFN is rather unexplored field compared to pharmacokinetics. IFN was initially advocated as a natural non-toxic antiviral substance. Many biological effects have been reported in experimental animals treated with IFN. Whether the side effects are due to the IFN molecule itself or to certain impurities present in the IFN preparation is a matter of conjecture. In this paper, the pharmacokinetics behavior, biological effects and toxicology of mouse and human IFN are reviewed.

Animals↗
PubMed1998

[Prostatectomy for prostate cancers].

Radical prostatectomy may afford cure in men in whom the malignancy is completely extirpable. Historical experiences as well as ours agreed that long term survival after radical prostatectomy was excellent if the disease was confined to the organ. Cure may also be expected in some selected patients with minimal extra-organ invasion. Furthermore, preoperative hormonal therapy may improve the cure rate in these invasive diseases. However, if cure means affording the patient the best chance of dying of some causes other than cancer, some of those extirpable diseases may be cured without surgery. This idea was supported by epidemiologic data on the natural history of the disease, and retrospective observations of conservatively treated patients. Challenging issues toward the 21st century are to expand the range of surgically curative diseases, and to identify diseases extirpable but predestined never to kill the host during the natural course of his life.

Aged↗
PubMed1998

[Considerations in rational use of tumor markers in breast carcinoma].

The objective of this review is to determine clinical practical guidelines for the use of serum tumor markers in the care of breast cancer patients outside of clinical trials. Mucin antigens (CA 15-3, MCA, CA 549) and CEA are established markers in breast cancer. Owing to their low sensitivity, none of these markers can be recommended for screening, diagnosis or staging. During follow-up, increasing marker levels may indicate recurrence 3-6 months earlier than clinical and radiological examinations in about 40-50% of patients. However, the clinical benefit of this lead-time is not established. Tumor markers are able to monitor response to treatment in 70-80% of patients with metastatic breast cancer. However, paradoxical changes of the markers especially in the beginning of treatment, the insufficient concordance with tumor activity in 20-30% of the women, and the lack of curative therapy regimens limit the prospective clinical use of the markers in the individual patient. Therefore, marker changes require confirmation by radiological methods in most cases. The present data are insufficient to recommend routine use of tumor markers alone for monitoring breast cancer patients after primary treatment or during palliative therapy. However, in the absence of readily measurable disease (e. g. bone metastases) continuously increasing marker levels may be used to indicate treatment failure. If high-dose chemotherapy in metastatic breast cancer renders to be effective, the clinical impact of tumor markers will increase considerably. Until that time, the analytical performance and the sensitivity of the established marker assays should be improved, and the clinical role of newer marker tests (TPS, CA 27.29) should be evaluated.

Biomarkers, Tumor↗
PubMed1999

[Standards, options and recommendations (SOR) for diagnosis, treatment and follow-up of osteosarcoma. Groupe de travail SOR].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of osteosarcoma in children and adult. METHODS: Data have been identified by literature search using Medline (1985-december 1998) and the expert groups personal reference lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of treatment. Once the guidelines were defined, the document was submitted for review to 27 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular, the 4 which have particular expertise in pediatric cancer management. RESULTS: The main recommendations for osteosarcoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and the biopsy should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical biopsy must be of adequate size and performed by an experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres. Inclusion of high dose methotrexate is recommended for children, and the dose of methotrexate must be adapted for adults. Inclusion of children in SFOP protocols and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases which may be curative. Amputation is rarely appropriate. Inclusion of children in SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition.

Antineoplastic Agents↗