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1.
Pragmat Obs Res ; 8: 211-222, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29066939

RESUMO

Chronic neuro-musculoskeletal pain is an important complication of open-heart surgery (OHS). To better understand the development and natural course of neuro-musculoskeletal pain in the immediate post-OHS period, this prospective longitudinal study assessed the prevalence and degree of pain and shoulder disability, and areas of pain pre- and post-OHS. Usual medical, nursing, and physiotherapy care was provided including early extubation, education, walking, sitting out of bed, and upper, lower limb, and trunk exercises from day 1 post-operation. Of 114 elective patients who provided consent, 98 subjects were surveyed preoperatively, and at week 6 and week 12 post-OHS. Open and closed questions encompassed numerical rating of pain scales for various body areas summed as a total pain score (TPS), the shoulder disability score (SDS), exercise compliance, and sternal clicking. Usual care comprised mobility exercises, walking program, and cardiac rehabilitation referral. Survey return rates were 100%, 88%, and 82%, respectively. Of the 76 (78%) subjects with complete data sets, 68% subjects reported a history of previous neuro-musculoskeletal injuries/conditions preoperatively while prevalence for neuro-musculoskeletal pain was 64%, 88%, and 67% and 38%, 63%, and 42% for shoulder disability, at the three assessments. In all, 11% subjects reported sternal clicking at week 6 and 7% at week 12. Pain commonly occurred in the lower back and neck preoperatively, and in front of the chest, neck, rib cage, upper back, and left shoulder at week 6. Rib cage pain alone remained significantly greater than preoperative levels by week 12 post-OHS. Preoperative SDS was positively correlated with post-OHS length of stay; women had higher SDSs than men at week 6 and week 12 and week 12 SDS was negatively correlated with height. Surgical risk score was negatively correlated with change in SDS and TPS from pre-operation to week 12. In conclusion, neuro-musculoskeletal pain and shoulder disability were common preoperatively and while prevalence increased at week 6 post-OHS, overall preoperative levels were restored by week 12.

2.
J Cardiopulm Rehabil Prev ; 35(6): 417-22, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26252344

RESUMO

PURPOSE: Home-based and center-based cardiac rehabilitation (CR) have demonstrated similar levels of risk factor reduction. Cardiac rehabilitation models with fewer exercise sessions may be as effective as traditional models. This study reviewed a community phase II CR database from 2007 to 2010. METHODS: A fast-track CR (FTCR) group was introduced alongside an existing traditional CR (TCR) program. The 2 programs ran concurrently on different days. Both FTCR and TCR treatment groups undertook supervised low to moderate intensity exercise training for 6 weeks and were provided with home exercise advice. Fast-track CR included once-weekly exercise sessions and a 1-time 7-hour education session; TCR included twice-weekly exercise and education sessions. Similar education was provided in both programs. Six-minute walk test distance (6MWD) was assessed pre-CR and post-CR for both groups. RESULTS: Six hundred and twenty patients enrolled in CR during the period, and patients elected or were assigned (not randomized) to FTCR (n = 197) or to TCR (n = 423) treatment groups. Complete 6MWD data sets were available for 115 FTCR and 254 TCR subjects. Repeated-measures analysis of variance found 6MWD outcomes to be similar for both groups over both assessments combined and at each assessment point. Improvements in 6MWD post-CR were different for men and women in the CR database (8% vs 5%, respectively, P < .001). CONCLUSIONS: Six-minute walk test distance outcomes were not different for subjects undergoing once-weekly or twice-weekly supervised CR exercise sessions. CR models with fewer supervised exercise sessions may provide similar functional outcomes to traditional CR models.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Teste de Esforço/estatística & dados numéricos , Terapia por Exercício/métodos , Terapia por Exercício/estatística & dados numéricos , Cardiopatias/reabilitação , Caminhada/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
J Cardiopulm Rehabil Prev ; 33(2): 99-105, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23221811

RESUMO

PURPOSE: To test the reliability of Timed Up and Go Tests (TUGTs) in cardiac rehabilitation (CR) and compare TUGTs to the 6-Minute Walk Test (6MWT) for outcome measurement. METHODS: Sixty-one of 154 consecutive community-based CR patients were prospectively recruited. Subjects undertook repeated TUGTs and 6MWTs at the start of CR (start-CR), postdischarge from CR (post-CR), and 6 months postdischarge from CR (6 months post-CR). The main outcome measurements were TUGT time (TUGTT) and 6MWT distance (6MWD). RESULTS: Mean (SD) TUGTT1 and TUGTT2 at the 3 assessments were 6.29 (1.30) and 5.94 (1.20); 5.81 (1.22) and 5.53 (1.09); and 5.39 (1.60) and 5.01 (1.28) seconds, respectively. A reduction in TUGTT occurred between each outcome point (P ≤ .002). Repeated TUGTTs were strongly correlated at each assessment, intraclass correlation (95% CI) = 0.85 (0.76-0.91), 0.84 (0.73-0.91), and 0.90 (0.83-0.94), despite a reduction between TUGTT1 and TUGTT2 of 5%, 5%, and 7%, respectively (P ≤ .006). Relative decreases in TUGTT1 (TUGTT2) occurred from start-CR to post-CR and from start-CR to 6 months post-CR of -7.5% (-6.9%) and -14.2% (-15.5%), respectively, while relative increases in 6MWD1 (6MWD2) occurred, 5.1% (7.2%) and 8.4% (10.2%), respectively (P < .001 in all cases). Pearson correlation coefficients for 6MWD1 to TUGTT1 and TUGTT2 across all times were -0.60 and -0.68 (P < .001) and the intraclass correlations (95% CI) for the speeds derived from averaged 6MWDs and TUGTTs were 0.65 (0.54, 0.73) (P < .001). CONCLUSIONS: Similar relative changes occurred for the TUGT and the 6MWT in CR. A significant correlation between the TUGTT and 6MWD was demonstrated, and we suggest that the TUGT may provide a related or a supplementary measurement of functional capacity in CR.


Assuntos
Teste de Esforço/métodos , Cardiopatias/reabilitação , Caminhada/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Reprodutibilidade dos Testes
4.
Physiotherapy ; 98(4): 277-86, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23122432

RESUMO

BACKGROUND: The 6-minute walk test (6MWT) is a common outcome measurement in cardiac rehabilitation. However, a search of the literature found no established guidelines for use of the 6MWT in cardiac rehabilitation. OBJECTIVES: Systematic review of the validity, reliability and responsiveness of the 6MWT in cardiac rehabilitation. DATA SOURCES: OvidMEDLINE, SPORTdiscus, EMBASE, CINAHL, Cochrane Reviews and Cochrane Clinical Trials between January 1948 and April 2011. ELIGIBILITY CRITERIA: Studies using 6MWTs in subjects with coronary artery disease undergoing cardiac rehabilitation on an outpatient basis, published in English, were included. STUDY APPRAISAL AND METHODS: Quantitative and qualitative analyses were conducted, including quality assessment of methodology, meta-analysis and assessment against level of evidence criteria. RESULTS: Fifteen articles met the inclusion criteria. One high-quality study was identified for reliability, six high-quality studies were identified for validity and 11 high-quality studies were identified for responsiveness. The meta-analysis found strong evidence that the 6MWT was responsive to change in clinical status following cardiac rehabilitation, with an estimated mean difference in 6-minute walk distance of 60.43m (95% confidence interval 54.57 to 66.30m; P<0.001). Qualitative analysis indicated moderate evidence for repeatability of the 6MWT in patients undergoing cardiac rehabilitation, for a 2% to 8% learning effect between repeated 6MWTs, for a relationship between peak heart rate during the 6MWT and during cycle exercise at the ventilatory threshold, and for moderate-to-high correlation between the 6-minute walk distance and maximum metabolic equivalents achieved on symptom-limited exercise tests. LIMITATIONS: Few studies assessed similar aspects of validity for the 6MWT. CONCLUSION: Strong evidence suggests that the 6MWT is responsive to clinical change following cardiac rehabilitation. Intra- and intertester reliability of the 6MWT and its validity in patients undergoing cardiac rehabilitation requires further research.


Assuntos
Assistência Ambulatorial/normas , Doença da Artéria Coronariana/reabilitação , Teste de Esforço/normas , Modalidades de Fisioterapia/normas , Caminhada , Humanos , Reprodutibilidade dos Testes
5.
Arch Phys Med Rehabil ; 92(9): 1388-94, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21878209

RESUMO

OBJECTIVE: To determine whether repeated 6-minute walk tests (6MWTs) are required for outcome measurement and exercise prescription in a typical cardiac rehabilitation (CR) population. DESIGN: Prospective longitudinal observational study. SETTING: Outpatient community health center. PARTICIPANTS: Sixty-one of 154 consecutive patients. INTERVENTION: 6MWTs (N = 2) were conducted at 3 assessment points: at CR start, postcompletion, and 6-months postcompletion. MAIN OUTCOME MEASURE: 6MWT distance (6MWD). RESULTS: Mean 6MWD for the first (6MWT1) and second (6MWT2) 6MWTs at the 3 assessment points were 507 ± 85 (522 ± 84), 532 ± 86 (560 ± 87), and 549 ± 99 (575 ± 107)m. Repeated 6MWDs strongly correlated at each assessment point, with intraclass correlation coefficients of .96 (95% confidence interval [CI], 0.93-.98), .97 (95% CI, .92-.98), and .94 (95% CI, .89-.97), respectively. Relative increases in mean 6MWD from 6MWT1 to 6MWT2 at each assessment point were 3%, 5%, and 5%, respectively (P<.001 in each case). Differences in walking speed derived from 6MWD1 and 6MWD2 did not translate into differences in exercise prescription. CONCLUSIONS: The difference between 6MWD1 and 6MWD2 was consistent regardless of previous exposure to 6MWTs. A single 6MWT was as effective as 2 repeated 6MWTs for outcome measurement and exercise prescription. We therefore recommend that when 6MWDs are used for CR outcome measurement, either a single 6MWT be used or the number of 6MWTs performed be consistent at all assessment points.


Assuntos
Reabilitação Cardíaca , Terapia por Exercício/métodos , Caminhada , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Resultado do Tratamento
6.
Ann Oncol ; 10(2): 223-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10093693

RESUMO

PURPOSE: This study was undertaken to evaluate the feasibility of administering docetaxel (Taxotere; Rhône-Poulenc-Rorer) as a one-hour intravenous (i.v.) infusion on day 1 combined with 5-fluorouracil (5-FU) as a bolus i.v. injection for five (days 1-5) or three (days 1-3) consecutive days every four weeks. PATIENTS AND METHODS: Thirty-seven patients with advanced solid malignancies were treated with 115 total courses involving seven dose levels of the two regimens of docetaxel and 5-FU (docetaxel/5-FU [mg/m2]/mg/m2/d]). In an effort to reduce fluid retention and hypersensitivity phenomena related to docetaxel, patients received premedication with dexamethasone 8 mg orally twice daily for three consecutive days beginning 24 hours before treatment. RESULTS: Severe (grade 4) neutropenia lasting longer than seven days with or without fever and/or severe mucositis, precluded further dose escalation above docetaxel 60 mg/m2 on day 1 and 5-FU 300 mg/m2/day administered on days 1-5 every four weeks. The rates of these toxic effects were also unacceptably high above docetaxel 60 mg/m2 on day 1 and 5-FU 300 mg/m2/day administered on days 1-3 every four weeks. Nine patients experienced various manifestations of fluid-retention that were potentially related to study drugs. However, neither treatment delay nor discontinuation of treatment was required. Nausea, vomiting, diarrhea, and fatigue, were mild to modest in severity and occurred infrequently (< 10% of courses). Two patients with metastatic breast cancer experienced complete responses and a partial response occurred in a patient with metastatic non-small-cell lung cancer. CONCLUSION: Based on the results of this study, the regimen of docetaxel 60 mg/m2 on day 1 followed by 5-FU 300 mg/m2/d i.v. for three or five days every four weeks is well tolerated and these doses are recommended for further evaluations. The feasibility of administering docetaxel 60 mg/m2 followed by 5-FU 300 mg/m2 for three or five days every four weeks and the preliminary antitumor activity noted indicate that further disease-directed studies of docetaxel and 5-FU are warranted in patients with relevant solid malignancies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Idoso de 80 Anos ou mais , Docetaxel , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
7.
Oncology (Williston Park) ; 11(6 Suppl 6): 33-5, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9213326

RESUMO

The relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days. To date, 27 patients with advanced solid neoplasms have received 86 courses of docetaxel/5-FU at the following dose levels: 25/100, 35/150, 50/200, 60/200, and 60/300 mg/m2. Preliminary results showed no unexpected toxicities, and the principal toxicity was neutropenia of short duration. A treatment regimen of 60 mg/m2 docetaxel on day 1 and 300 mg/m2 of 5-FU given for 5 days, with a single course length of 28 days, is projected as the maximum tolerated dose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivados
8.
J Clin Oncol ; 13(12): 2879-85, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8523050

RESUMO

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS: Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS: Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION: Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.


Assuntos
Antraciclinas/farmacologia , Antraquinonas/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico
9.
J Clin Oncol ; 13(12): 2886-94, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8523051

RESUMO

PURPOSE: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico
10.
Int J Cancer ; 50(4): 553-6, 1992 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-1537621

RESUMO

Our experience with the combination of dacarbazine, carmustine, cisplatin with and without tamoxifen is reported. In our initial study, with all 4 drugs, we had an overall response rate of 50% with a complete response rate of 15%. Due to a high incidence of deep venous thrombosis and the lack of effectiveness of tamoxifen as a single agent, we deleted tamoxifen from the regimen and treated another 20 patients. Surprisingly, the response rate decreased to 10%. We then re-incorporated tamoxifen into the regimen and treated 25 additional patients. In this third group of patients we experienced an objective response rate of 52% with a complete response rate of 8%. Overall, 65 patients have been treated: 45 with and 20 without tamoxifen. Twenty-three (51%) patients treated with tamoxifen have responded, with 5 (11%) patients achieving a complete response. Only 2 (10%) patients treated without tamoxifen have responded. Despite the improvement in the response rate, a corresponding increase in survival has not been seen. Patients treated with tamoxifen had a mean survival of 10.8 (SD 13.6) months compared with a mean survival of 9.8 (SD 7.3) months for those treated without tamoxifen. The absence of survival advantage for the tamoxifen-treated patients may be due to early failure in the central nervous system. In 48% of the responding tamoxifen-treated patients, the first site of failure was the central nervous system, while systemic disease was still responding.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Tamoxifeno/administração & dosagem , Adulto , Idoso , Cisplatino/administração & dosagem , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica
12.
Cell ; 58(6): 1155-62, 1989 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-2570641

RESUMO

Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP. We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides. A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe. The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain. Cyclic GMP concentrations in cells transfected with GC-A were half-maximally elevated at 3 nM ANP, 25 nM brain natriuretic peptide (BNP), and 65 nM atriopeptin 1, while 25 microM ANP, 6 microM BNP, and greater than 100 microM atriopeptin 1 were required for half-maximal stimulation of GC-B. The potencies of natriuretic peptides on GC-A and GC-B activity are therefore markedly different; furthermore, despite the specificity of GC-B for BNP, the relatively high BNP concentration required to elicit a response suggests the possible presence of a more potent, unidentified natural ligand.


Assuntos
Genes , Guanilato Ciclase/genética , Família Multigênica , Receptores de Superfície Celular/genética , Sequência de Aminoácidos , Animais , Fator Natriurético Atrial/metabolismo , Sequência de Bases , Encéfalo/enzimologia , Linhagem Celular , Membrana Celular/enzimologia , Clonagem Molecular , DNA/genética , Variação Genética , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Ratos , Receptores do Fator Natriurético Atrial , Homologia de Sequência do Ácido Nucleico , Transfecção
13.
Proc Natl Acad Sci U S A ; 86(7): 2128-32, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2538832

RESUMO

An apparent receptor for the egg peptide speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) was identified by covalently coupling a radiolabeled speract analogue to intact spermatozoa and was then purified by DEAE-Sepharose chromatography and preparative gel electrophoresis after solubilization with Lubrol PX. The purified, crosslinked protein was digested with Staphylococcus aureus V8 protease and a resultant peptide, purified from polyacrylamide slab gel slices, was shown to have the amino acid sequence Val-Ser-Ala-Pro-Phe-Asp-Leu-Glu-Ala-Pro-Phe-Ile-Ile-Asp-Gly-Ile. Polyclonal antiserum, generated against a synthetic peptide that corresponded to the above sequence, immunoprecipitated the radiolabeled crosslinked protein and reacted with a Mr 77,000 protein on immunoblots, demonstrating that the sequenced peptide originated from the apparent receptor. A clone containing a 2.5-kilobase insert was subsequently isolated from a sea urchin testis cDNA library that contained DNA sequences encoding an open reading frame of 532 amino acids that included the above peptide sequence. The deduced amino acid sequence suggests that the protein contains a 26-residue amino-terminal signal peptide, a large extracellular domain relatively rich in cysteine (5%) that includes a four-fold repeat of about 115 amino acids, a single membrane-spanning region, and only 12 amino acid residues extending into the cytoplasm. Analysis of total RNA from Strongylocentrotus purpuratus testis by Northern blot revealed a 2.5-kilobase RNA. Preliminary data show the presence of hybridizing RNA of the same apparent size in other sea urchin species, including Arbacia punctulata, which does not respond to speract.


Assuntos
Clonagem Molecular , Oligopeptídeos/metabolismo , RNA Mensageiro/genética , Receptores de Superfície Celular/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Reagentes de Ligações Cruzadas , Feminino , Masculino , Dados de Sequência Molecular , Peso Molecular , Receptores de Superfície Celular/isolamento & purificação , Receptores de Superfície Celular/metabolismo , Sequências Repetitivas de Ácido Nucleico , Mapeamento por Restrição , Ouriços-do-Mar , Interações Espermatozoide-Óvulo
14.
Cancer ; 63(7): 1292-5, 1989 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-2920358

RESUMO

The combination of dacarbazine (DTIC, 220 mg/m2) and cisplatin (DDP, 25 mg/m2) IV daily for 3 days every 3 weeks, carmustine (BCNU, 150 mg/m2) IV every 6 weeks, and tamoxifen (TAM, 10 mg orally twice daily) produced a 50% objective response rate in patients with metastatic melanoma. Associated with this treatment, there was a high incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). In an effort to reduce this toxicity, this regimen minus TAM was studied, and the results are reported. Twenty of twenty patients are evaluable for response and toxicity. There was one complete response (CR) lasting 5+ months and one partial response (PR) lasting 4+ months for an overall response rate of 10% (95% confidence limits, 1.23% to 31.70%). Two patients exhibited a mixed response and three patients developed disease stabilization lasting 4 to 10 months. Toxicity was similar to the original study except that no patients developed DVT or PE. This statistically significant (Fisher's exact test [two-tail] P = 0.008) decrease in the response rate by comparison with that achieved with the TAM-containing regimen may signal an essential role of TAM in this regimen. TAM may be acting in synergy with cisplatin through its calcium channel-blocking properties. TAM should be included as described in the initial reports, and the patients should be carefully observed for vascular complications.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/induzido quimicamente , Tamoxifeno/efeitos adversos , Tromboflebite/induzido quimicamente
15.
Med Clin North Am ; 71(3): 529-40, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3553776

RESUMO

This chapter has served to highlight many of the important medical problems seen in the oncology patient. These problems stem from the effects of malignancy itself as well as from treatment. An overall understanding of these disorders and their management is essential to the proper preoperative evaluation of the cancer patient.


Assuntos
Neoplasias/cirurgia , Cuidados Pré-Operatórios , Humanos , Neoplasias/complicações , Neoplasias/diagnóstico
16.
Cancer Treat Rep ; 71(5): 465-9, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3567970

RESUMO

Twenty-three patients with metastatic melanoma were treated with combination therapy consisting of dacarbazine (220 mg/m2) and cisplatin (25 mg/m2) iv daily for 3 days every 3 weeks, carmustine (150 mg/m2) iv every 6 weeks, and tamoxifen (10 mg) orally twice daily. In 20 evaluable patients, there were no complete responses and ten partial responses. The median remission duration has not yet been reached but exceeds 7 months. Treatment was relatively well tolerated. However, six patients developed deep venous thrombosis, and four of these six suffered pulmonary emboli. Our data support a previous study and suggest that this combination warrants comparison with the active single components in a randomized prospective trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Nefropatias/induzido quimicamente , Leucopenia/induzido quimicamente , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Tamoxifeno/administração & dosagem , Trombocitopenia/induzido quimicamente , Tromboembolia/induzido quimicamente , Vômito/induzido quimicamente
17.
Ann Surg ; 205(1): 88-9, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3800466

RESUMO

A retrospective study of the medical records of 102 patients with Stage II malignant melanoma was conducted to determine the frequency of occult residual melanoma after excision of a clinically positive regional lymph node. Twenty-one patients met the study criteria for evaluation. Fifteen of 22 dissections were positive for melanoma (68.1%). These results support definitive regional lymph node dissection if the results of excisional biopsy are abnormal. No conclusions can be drawn from these data regarding the survival advantage of therapeutic regional lymph node dissection.


Assuntos
Excisão de Linfonodo , Linfonodos/patologia , Melanoma/diagnóstico , Humanos , Metástase Linfática , Estudos Retrospectivos
18.
Biochim Biophys Acta ; 812(3): 695-701, 1985 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-2857574

RESUMO

The purified membrane-bound form of guanylate cyclase was incorporated into artificial unilamellar phospholipid vesicles. The rate and extent of enzyme incorporation into the vesicles was dependent upon the phospholipid concentration and the time period of incubation. The enzyme was incorporated at a significantly faster rate after removal of carbohydrate with endoglycosidase H. The incorporation of the enzyme led to a 10-fold decrease in the apparent maximal velocity and a 2-fold increase in the apparent Michaelis constant for MnGTP. Extraction of liposomes containing guanylate cyclase with 0.2% Lubrol PX resulted in the recovery of 85% of the original amount of added activity, suggesting that the decrease in maximal velocity was not due to enzyme denaturation. Phosphatidylcholine liposomes differentially effected the activity of the membrane-form of guanylate cyclase, dependent on the nature of the fatty acid present on the phospholipid. Specific activities ranged between 458 nmol/min per mg and 2.6 mumol/min per mg, dependent upon the fatty acids present. Liposomes containing the membrane-bound form of guanylate cyclase were subsequently fused with erythrocytes using poly(ethylene glycol) 4000 in attempts to introduce the enzyme into intact cells. The enzyme was successfully introduced into the erythrocytes; greater than 90% of the enzyme activity was subsequently shown to be associated with erythrocyte membranes. Cyclic GMP concentrations of erythrocytes increased from essentially nondetectable to 4 pmol/10(9) cells after introduction of the enzyme. These results demonstrate that guanylate cyclase can be incorporated into liposomes in an active state and that such liposomes can be used to introduce the enzyme into cells where it can subsequently function to generate cyclic GMP.


Assuntos
Eritrócitos/enzimologia , Guanilato Ciclase/metabolismo , Lipossomos/metabolismo , GMP Cíclico/biossíntese , Ácidos Graxos/análise , Guanilato Ciclase/imunologia , Humanos , Soros Imunes , Cinética , Fosfolipídeos/farmacologia , Relação Estrutura-Atividade
20.
Am J Ophthalmol ; 89(4): 567-70, 1980 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7369321

RESUMO

A patient with malignant melanoma of the choroid and ciliary body had a primary cutaneous melanoma and the B-K mole syndrome phenotype. Because of this newly described association, all patients with the B-K mole syndrome (phenotype) should have a complete ocular examination to discover if there is any evidence of ocular melanoma. Likewise, all patients with ocular melanoma should have a thorough dermatologic examination to determine evidence of cutaneous melanoma and the B-K mole syndrome (phenotype).


Assuntos
Neoplasias da Coroide/genética , Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Nevo Pigmentado/genética , Neoplasias Cutâneas/genética , Neoplasias da Coroide/cirurgia , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/cirurgia , Síndrome
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