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At least 433 records · Page 24Linked to original sources
PubMed2004

HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.

Adolescent↗
PubMed1997

When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications.

When to suspect and thus investigate for inborn errors of purine and pyrimidine metabolism is a dilemma for even the most observant investigator. Often parents of affected children, or a history involving siblings, can provide valuable clues. The recognition of new purine and pyrimidine disorders requires skill and serendipity. But even identifying known disorders can prove difficult, since they cover a broad spectrum of illnesses, can have more than one symptom, or lead to early death. This problem is compounded by the fact that they are relatively recently described and therefore often little known, either in the clinic or laboratory. The considerable heterogeneity in clinical expression within families as well as between families means that asymptomatic homozygotes may not be recognized or can present at any time from early childhood through adolescence up to their eighth decade. Consequently, all siblings should be screened. These disorders should be suspected in any case of unexplained anaemia, failure to thrive, susceptibility to recurrent infection, or neurological deficits with no current diagnosis, including autism, cerebral palsy, delayed development, deafness, epilepsy, self-mutilation, muscle weakness, the inability to walk or talk, and-unusual in children and adolescents-gout, sometimes with renal disease. Some disorders present with radiolucent kidney stones, in acute or chronic renal failure, alone or with any of the above, or as an intolerance/sensitivity to therapy (e.g. 5-fluorouracil in malignancies or azathioprine immunosuppression in organ transplantation), often with life-threatening consequences. Several parameters need to be evaluated to ensure correct diagnosis. Pitfalls which can mask diagnosis using only a single test are renal failure, blood transfusion, diet or drugs.

Biomarkers↗
PubMed1995

Orchiectomy after chemotherapy in patients with metastatic testicular cancer. Is it indicated?

BACKGROUND: A small proportion of patients with testicular germ cell tumors present with widely metastatic disease and are treated initially with chemotherapy. Little is known about the efficacy of systemic chemotherapy in eradicating the primary testicular germ cell cancer; however, there is concern that the testis may act as a sanctuary site for germ cell cancer in these patients, and orchiectomy, is, therefore, recommended after chemotherapy. METHODS: The results from a clinical and pathologic review of 24 patients who underwent delayed orchiectomy after chemotherapy are presented. The testicular pathologic findings are correlated with those in extragonadal masses and also with a blinded review of postchemotherapy testicular ultrasound scans. RESULTS: The most common testicular pathological finding was a dense fibrous scar that was found in all patients. Three patients had persistent testicular germ cell cancer, six had mature teratoma, and one had carcinoma in situ. There was a strong concordance between the major testicular pathologic findings and those in the resected extragonadal masses. All three patients with persistent testicular germ cell cancer subsequently had disease progression in the extragonadal sites. Testicular ultrasound examination did not distinguish accurately between residual tumor or scar in the testis. CONCLUSION: Persistence of the primary testicular germ cell cancer is most likely due to the same heterogeneous response to chemotherapy observed in different metastatic sites. Because current imaging techniques cannot identify accurately those patients with residual testicular germ cell cancer or related testicular abnormalities that may predispose to subsequent relapse, orchiectomy after chemotherapy remains appropriate.

Adult↗
PubMedDate not supplied

Lack of transmission of hepatitis C virus following needlestick accidents.

Healthcare workers (HCWs) have an occupational risk of infection with hepatitis C virus (HCV). However, data regarding the magnitude of this risk are limited. We conducted a prospective study on a cohort of 24 HCWs who were exposed to HCV by needlestick injuries involving 25 patients. All source patients were viremic with a mean HCV-RNA level of 1.65 megagenomic equivalents per milliliter. At least 64% of patients were infected with HCV serotype 4 (Simmond's classification). After a follow up period of at least 6 months, none of the exposed HCWs acquired HCV. Thus, HCV does not seem to be easily transmitted by needlestick injuries. However, further large-scale studies are needed for a more accurate estimation of the risk of transmission.

Accidents, Occupational↗
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed1998

The effect of treatment with alpha-interferon on hepatitis G/GBV-C viraemia. The CONSTRUCT Group.

BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to alpha-interferon treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses.

Adult↗
PubMed1998

Prevalence, incidence, and clinical characteristics of hepatitis G virus/GB virus C infection in Scottish blood donors.

The prevalence, incidence, clinical features, and natural history of hepatitis G virus (HGV) or GB virus C (GBV-C) were investigated in a non-remunerated blood donor population to determine its clinical significance and its impact on blood safety. Of 1020 regular blood donors, 23 (2.25%) were positive for plasma HGV/GBV-C RNA. Alanine aminotransferase levels were lower than in uninfected donors (median, 20 IU/mL; 32 IU/mL in controls; P=.015). Clinical examination produced no other evidence for hepatitis or for shared nonhepatic diseases. Fifteen of 17 donors excreted HGV/GBV-C in saliva (mean level, 8x103 copies of RNA/mL). Testing of previous donations indicated an incidence of 170-200 new infections with HGV/GBV-C per 100,000 donor-years. The absence of further clinicopathologic data and the limitations of current polymerase chain reaction-based methods for screening suggests that it is neither necessary nor practical to commence screening.

Adult↗
PubMed1994

Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs.

The frequency and dynamics of infection with different genotypes of hepatitis C virus were investigated in a cohort of hemophiliacs repeatedly exposed to non-virus-inactivated clotting factor. Among 63 infected hemophiliacs, genotype 1 (n = 38, subtypes 1a [27] and 1b [11]) was predominant; genotypes 2a (n = 1), 2b (n = 3), 3a (n = 20), and 5a (n = 1) accounted for the remainder. This distribution was similar to that found in Scottish blood donors from whom the infected blood products were manufactured. Hemophiliacs with severe disease were more likely to be polymerase chain reaction-positive than those with moderate or mild disease. Over 10 years, changes in the circulating major genotype and serotype were observed in 9 of 29 hemophiliacs and from one subtype to another in 3, although there was no clear trend toward replacement with any particular variant. Replacement occurred after the introduction of inactivated clotting factor in 4 subjects, implicating reactivation rather than reinfection. Those coinfected with human immunodeficiency virus were more likely to show a change in genotype.

Blood Donors↗
PubMed1991

Detection, quantification and sequencing of HIV-1 from the plasma of seropositive individuals and from factor VIII concentrates.

A highly sensitive and reliable RNA polymerase chain reaction method has been developed which has been used to detect, quantify and sequence cell-free HIV RNA directly from the plasma of seropositive individuals. Plasma from 10 out of 12 haemophiliacs tested was found to contain detectable levels of HIV-1 RNA [log mean value: 1.2 x 10(3) copies for Centers for Disease Control (CDC) group II patients, 5.5 x 10(3) copies for CDC group IV patients]. The presence of cell-free circulating virus in both symptomatic and asymptomatic individuals suggests that viral replication continues throughout the course of infection. The same procedure has been used to detect and sequence HIV-1 RNA in two batches of unheated commercial factor VIII concentrate distributed in 1981 and 1983. The sequences obtained revealed a closer relationship to North American than to African strains of HIV-1.

Amino Acid Sequence↗
PubMed1999

Combined adenine phosphoribosyltransferase and N-acetylgalactosamine-6-sulfate sulfatase deficiency.

We describe a Czech patient with combined adenine phosphoribosyltransferase (APRT) deficiency (2,8-dihydroxyadenine urolithiasis) and N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency (mucopolysaccharidosis Type IVA, Morquio disease A). Adenine and its extremely insoluble derivative, 2,8-dihydroxyadenine, were identified in the urine, and APRT deficiency was confirmed in erythrocytes. There was excessive excretion of keratan sulfate in the urine, and GALNS deficiency was confirmed in leukocytes. GALNS and APRT are both located on chromosome 16q24.3, suggesting that the patient had a deletion involving both genes. PCR amplification of genomic DNA indicated that a novel junction was created by the fusion of sequences distal to GALNS exon 2 and proximal to APRT exon 3, and that the size of the deleted region was approximately 100 kb. The deletion breakpoints were localized within GALNS intron 2 and APRT intron 2. Several other genes, including the alpha subunit of cytochrome B (CYBA), which is deleted or mutated in the autosomal form of chronic granulomatous disease, are located in the 16q24.3 region, but PCR amplification showed that this gene was present in the proband. A patient with hemizygosity for GALNS deficiency and APRT deficiency has been reported from Japan recently. These findings indicate that: (i) APRT is located telomeric to GALNS; (ii) GALNS and APRT are transcribed in the same orientation (centromeric to telomeric); and (iii) combined APRT/GALNS deficiency may be more common than hitherto realized.

Adenine Phosphoribosyltransferase↗
PubMedDate not supplied

Clinical uses of mifepristone: an update for women's health practitioners.

In September 2000, the U.S. Food and Drug Administration (FDA) approved the use of mifepristone for the provision of medical abortion. Although mifepristone was developed and marketed because of its potential to effect early first-trimester medical abortion, it has additional applications to health care, including the treatment of gynecologic conditions, cancer, and Cushing's disease. The controversial nature of abortion has dominated the publicity about mifepristone. The evidence for the safety and efficacy of mifepristone in medical abortion has been overshadowed, and many clinicians are unaware of the other potential uses of the drug. This article provides a discussion of background information on the pharmacology, development of, and research on mifepristone and an update on current and potential uses in health care today. Information on the FDA-approved regimen and alternative protocols for management of mifepristone in its use in abortion care are presented.

Abortifacient Agents, Steroidal↗
PubMed2006

Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi.

The methanol extract of stems of Catalpa ovata G Don exhibits potent in vivo antifungal activity against Magnaporthe grisea (Hebert) Barr (rice blast) on rice plants, Botrytis cinerea Pers ex Fr (tomato grey mould) and Phytophthora infestans (Mont) de Bary (tomato late blight) on tomato plants, Puccinia recondita Rob ex Desm (wheat leaf rust) on wheat plants and Blumeria graminis (DC) Speer f. sp. hordei Marchal (barley powdery mildew) on barley plants. An antifungal substance was isolated and identified as dehydro-alpha-lapachone from mass and nuclear magnetic resonance spectral data. It completely inhibited the mycelial growth of B. cinerea, Colletotrichum acutatum Simmonds, Colletotrichum gloeosporioides Simmonds, M. grisea and Pythium ultimum Trow over a range of 0.4-33.3 mg litre(-1). It also controlled the development of rice blast, tomato late blight, wheat leaf rust, barley powdery mildew and red pepper anthracnose (Colletotrichum coccodes (Wallr) S Hughes). The chemical was particularly effective in suppressing red pepper anthracnose by 95% at a concentration of 125 mg litre(-1).

Bignoniaceae↗
PubMed1987

A randomized trial of aminoglutethimide +/- estrogen before chemotherapy in advanced breast cancer.

Recent reports have suggested that the sensitivity to chemotherapy of endocrine-dependent breast cancer may be enhanced by transient exposure to hormonal stimulation. To test this concept, 39 postmenopausal women with proven metastatic breast carcinoma and measurable disease were entered into this prospective, double-blind trial; 35 are currently evaluable. All patients were continuously treated with aminoglutethimide and hydrocortisone to lower estrogen production, plus cyclic chemotherapy. Patients in the "stimulation" arm received in addition, Estrace 2 mg b.i.d. sublingually for 3 days before and on the day of chemotherapy. Estrace administration appeared to accelerate tumor growth as demonstrated by increased bone pain, hypercalcemia, and growth of skin lesions. Response rates, response duration, and survival were similar in the stimulation and control groups.

Aminoglutethimide↗
PubMed2005

Pyrimidine pathways in health and disease.

Genetic defects involving enzymes essential for pyrimidine nucleotide metabolism have provided new insights into the vital physiological functions of these molecules in addition to nucleic acid synthesis. Such aberrations disrupt the haematological, nervous or mitochondrial systems and can cause adverse reactions to analogue therapy. Regulation of pyrimidine pathways is also known to be disrupted in malignancies. Nine genetic defects have now been identified but only one is currently treatable. Diagnosis is aided by the accumulation of specific metabolites. Recently, progress has been made in understanding the molecular mechanisms underlying inborn errors of pyrimidine metabolism, together with the key clinical issues and the implications for the future development of novel drugs and therapeutic strategies.

Health↗
PubMed1997

Pain management guidelines: implications for managed care--a roundtable discussion.

One of the most important concerns of patients with cancer, particularly those with metastatic disease, is "Will I be in constant pain?" This is a similar concern voiced by patients with late-stage human immunodeficiency virus infection. The management of chronic pain has enormous implications on a patient's ability to function and on his or her quality of life. In June 1996, Medical Interface convened a panel of experts in Chicago to discuss pain management therapies, guidelines, and how these issues will affect, and be affected by, the managed care environment.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Importance of the human erythrocyte in the diagnosis of inherited purine and pyrimidine disorders.

The intact erythrocyte has proved invaluable in the diagnosis of inherited purine and pyrimidine disorders. Not only can it be used to establish the integrity of a particular pathway where enzyme activity is undetectable in disrupted cells, the characteristic alterations in nucleotide patterns in some disorders have provided valuable insight into the mechanism by which the abnormal gene product produces disease. The severe GTP depletion associated with neurological deficits may mirror the situation in the brain, which like the erythrocyte is largely dependent on salvage to sustain its GTP levels. The ability of analogues to accumulate in erythrocytes may likewise give some clue as to the metabolic basis for the associated clinical manifestations, or the efficacy of a particular drug. In addition to their use in determining prognosis as well as providing a diagnosis, such studies have enabled demonstration of a novel route of ATP formation in human cells. The above changes may be masked if immediate processing is not possible.

Adenosine Triphosphate↗
PubMed2006

Radiotherapy: a novel treatment for pneumothorax.

Pneumothorax is a relatively common condition that is usually managed either conservatively, by chest tube drainage or, if a refractory air leak persists, then with cardiothoracic intervention. However, there is a small group of patients with a persistent air leak in whom surgical intervention is felt to be inappropriate. This study looks at a novel management strategy in a patient presenting with this scenario. A male with underlying bullous lung disease presented with a right pneumothorax. Complete re-expansion was not achieved, despite chest tube drainage and suction. Cardiothoracic intervention was felt to be inappropriate and the air leak persisted despite prolonged conservative management. Ventilation scintigraphy was therefore used to localise the air leak prior to targeted radiotherapy in an attempt to seal the leak via radiation-induced fibrosis. Three weeks after the first fraction of radiotherapy, the air leak ceased. In complex cases of pneumothorax with persistent air leak where cardiothoracic intervention is deemed inappropriate, identification of the air leak site and localised radiotherapy could be considered.

Adult↗
PubMedDate not supplied

Hormone stimulation and chemotherapy in advanced prostate cancer: preliminary results of a prospective controlled clinical trial.

Preliminary evidence suggests that the sensitivity of endocrine-dependent neoplasms to chemotherapy may be enhanced by transient hormonal stimulation of tumor growth. To test this concept, we are conducting a prospective controlled trial in men with stage D2 prostate cancer who have relapsed following orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion plus cyclic chemotherapy. Patients in the stimulation arm receive, in addition, the synthetic androgen fluoxymesterone for 3 days before and on the day of chemotherapy. Of 41 patients entered to date, 26 are evaluable. Twenty-one (81%) obtained either an objective remission or stabilization of disease with a mean duration of 9+ months and 10 patients still responding. Thus far, the response rate is similar in the control and stimulation groups. Androgen administration was associated with a rise in acid phosphatase and usually a modest flare of symptoms except for 2 patients who developed spinal cord compression. These preliminary data indicate that the combination of aminoglutethimide and chemotherapy has a potent antitumor effect on advanced prostate cancer refractory to orchiectomy. A large number of patients and a longer follow up are needed to assess whether transient androgen administration potentiates the effect of chemotherapy.

Acid Phosphatase↗