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At least 235 records · Page 13Linked to original sources
PubMed2003

A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up.

OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.

Aged↗
PubMed2006

Local stakeholders' perspectives on improving the urban environment to reduce child pedestrian injury: implementing effective public health interventions at the local level.

Local-level public health interventions require action from multiple agencies, organizations and individuals, yet little is known about how best to work with stakeholders to facilitate change. We sought local stakeholders' perspectives on how best to address impediments to implementing interventions designed to reduce child pedestrian injury by improving the pedestrian environment. We conducted 20 in-person, key informant interviews with people who would be the likely advocates for environmental change to improve the pedestrian environment in one US city, Baltimore, Maryland. We discuss the importance of reframing child pedestrian injury risk as a livability issue, increasing awareness about the potential impact of environmental changes to improve public safety, and the need for a formal efficient process to facilitate communication between local government and other stakeholders. These findings provide public health professionals and advocates with useful insight into how local stakeholders view the issue and their perspectives on how best to achieve change.

Accidents, Traffic↗
PubMed1991

A yeast protein that binds nuclear localization signals: purification localization, and antibody inhibition of binding activity.

Short stretches of amino acids, termed nuclear localization sequences (NLS), can mediate assembly of proteins into the nucleus. Proteins from the yeast, Saccharomyces cerevisiae, have been identified that specifically recognize nuclear localization peptides (Silver, P., I. Sadler, and M. A. Osborne. 1989. J. Cell Biol. 109:983-989). We now further define the role of one of these NLS-binding proteins in nuclear protein localization. The NLS-binding protein of 70-kD molecular mass can be purified from salt extracts of nuclei. Antibodies raised against the NLS-binding protein localized the protein mainly to the nucleus with minor amounts in the cytoplasm. These antibodies also inhibited the association of NLS-protein conjugates with nuclei. Incubation of nuclei with proteases coupled to agarose removed NLS-binding protein activity. Extracts enriched for NLS-binding proteins can be added back to salt or protease-treated nuclei to restore NLS-binding activity. These results suggest that the first step of nuclear protein import can be reconstituted in vitro.

Amino Acid Sequence↗
PubMed1994

M-VAC combination in locally advanced, locally recurrent or metastatic breast carcinoma. A phase II study.

BACKGROUND: The M-VAC combination is very effective in bladder carcinoma, as are all four drugs, as single-agent, in advanced breast carcinoma. PATIENTS AND METHODS: M-VAC was given in 27 patients, 4 with locally advanced breast carcinoma, 3 with local recurrence and 20 with distant metastases. The median age was 51 (range 25; 70). Eleven of the 20 patients with metastatic disease has been previously treated with a different chemotherapy. RESULTS: 15 of 26 evaluable patients responded, with 9 (35%) complete remissions and 6 partial responses. The overall response rate (CR plus PR) was 57% (95% confidence interval 38% to 76%). In patients with metastatic disease the median duration of response was 7 months (range 4+; 36+), median time to progression 5 months (range 1; 36+) and median duration of survival 17 months (range 1; 40+). CONCLUSION: The M-VAC combination is very effective in locally advanced, locally recurrent and metastatic breast carcinoma. Further trials are warranted to evaluate whether the activity of this combination is partially schedule-dependent.

Adult↗
PubMed1991

Local-regional recurrences of breast cancer: treatment with radiation therapy and local microwave hyperthermia.

From October 1981 through September 1988, 31 local-regional recurrences of breast cancer in 26 patients were treated at the Oncology Center in Trento, Italy, with a combination of external radiation therapy (XRT) and superficial local microwave hyperthermia (Ht). The mean total XRT dose was 37.40 Gy, ranging from 19.80 to 60.00 Gy, depending on the extent of previous irradiation. Ht was delivered using the same superficial mw applicator, operating at frequencies between 280 and 480 MHz. The goal was to obtain a minimum intra- and peritumoral temperature of 42.5 degrees C for 30 min. Ht was applied immediately after XRT, 2 or 3 times per week for a total of 1-9 sessions (median 2). Thirty lesions (97%) could be evaluated for response 3 months after the end of the combined treatment. Twenty (66.6%) complete responses, seven (23.3%) partial responses, and three (10%) with no change were observed. No significant acute local side effects were noted, with the exception of two thermal burns and one ulceration. Patients achieving complete response show actuarial long-term local control of 87.8% at 3 years. In our experience, Ht combined with a low/moderate XRT dose may be particularly valuable in the palliation of recurrences in previously irradiated regions. Excellent response rates can be obtained when Ht is combined with a radical dose of irradiation.

Aged↗
PubMed2006

Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumor-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival.

OBJECTIVE: The purpose of this study was to determine the oncologic outcomes and clinical factors affecting survival in patients who underwent neoadjuvant chemoradiotherapy following tumor specific mesorectal excision for locally advanced, fixed rectal cancer. SUMMARY BACKGROUND DATA: Neoadjuvant chemoradiation therapy has resulted in significant tumor downstaging, which enhances curative resection and subsequently improves local disease control for rectal cancer. However, oncologic outcomes, according to clinical factors, have not yet been fully understood in locally advanced and fixed rectal cancer. METHODS: A total of 114 patients who had undergone neoadjuvant chemoradiation for advanced rectal cancer (T3 or T4 and node positive) were investigated retrospectively. Chemotherapy was administered intravenously with 5-FU and leucovorin during weeks 1 and 5 of radiotherapy. The total radiation dose was 5040 cGY in 25 fractions delivered over 5 weeks. Tumor-specific mesorectal excision was done 4 to 6 weeks after the completion of neoadjuvant chemoradiation. Survival and recurrence rates, according to the pathologic stage, were evaluated. Moreover, factors affecting survival were investigated. RESULTS: The 5-year survival rates according to pathologic stage were: 100% in pathologic complete remission (n = 10), 80% in stage I (n = 23), 56.8% in stage II (n = 34), and 42.3% in stage III (n = 47) (P = 0.0000). Local, systemic, and combined recurrence rates were 11.4%, 22.8%, and 3.5%, respectively. Multivariate analysis showed that the pathologic N stage and operation method were the independent factors affecting survival rate. CONCLUSION: Pathologic complete remission showed excellent oncologic outcomes, and the pathologic N stage was the most important factor for oncologic outcomes.

Adult↗
PubMed2000

The effect of local anaesthetic spray on the pain associated with local anaesthetic injection, prior to biopsy or loop diathermy to the cervix in the outpatient colposcopy clinic.

We evaluated the effectiveness of local anaesthetic spray prior to injection of local anaesthetic before biopsy or large loop excision of the transformation zone of the cervix at colposcopy. This was a prospective, randomised, double-blind placebo-controlled study involving 51 women. Pain or discomfort was measured using a four-point categorical scale and a visual analogue score. Our results show that the use of local anaesthetic spray has no effect on the pain or discomfort experienced by patients having local anaesthetic injections to the cervix, and cannot be recommended.

Adult↗
PubMed2002

Human cytomegalovirus UL84 localizes to the cell nucleus via a nuclear localization signal and is a component of viral replication compartments.

The UL84 open reading frame encodes a protein that is required for origin-dependent DNA replication and interacts with the immediate-early protein IE2 in lytically infected cells. Transfection of UL84 expression constructs showed that UL84 localized to the nucleus of transfected cells in the absence of any other viral proteins and displayed a punctate speckled fluorescent staining pattern. Cotransfection of all the human cytomegalovirus replication proteins and oriLyt, along with pUL84-EGFP, showed that UL84 colocalized with UL44 (polymerase accessory protein) in replication compartments. Experiments using infected human fibroblasts demonstrated that UL84 also colocalized with UL44 and IE2 in viral replication compartments in infected cells. A nuclear localization signal was identified using plasmid constructs expressing truncation mutants of the UL84 protein in transient transfection assays. Transfection assays showed that UL84 failed to localize to the nucleus when 200 amino acids of the N terminus were deleted. Inspection of the UL84 amino acid sequence revealed a consensus putative nuclear localization signal between amino acids 160 and 171 (PEKKKEKQEKK) of the UL84 protein.

Animals↗
PubMed2005

Human mRNA cap methyltransferase: alternative nuclear localization signal motifs ensure nuclear localization required for viability.

A characteristic feature of gene expression in eukaryotes is the addition of a 5'-terminal 7-methylguanine cap (m7GpppN) to nascent pre-mRNAs in the nucleus catalyzed by capping enzyme and cap methyltransferase. Small interfering RNA (siRNA) knockdown of cap methyltransferase in HeLa cells resulted in apoptosis as measured by terminal deoxynucleotidyltransferase-mediated dUTP-tetramethylrhodamine nick end labeling assay, demonstrating the importance of mRNA 5'-end methylation for mammalian cell viability. Nuclear localization of cap methyltransferase is mediated by interaction with importin-alpha, which facilitates its transport and selective binding to transcripts containing 5'-terminal GpppN. The methyltransferase 96-144 region has been shown to be necessary for importin binding, and N-terminal fusion of this sequence to nonnuclear proteins proved sufficient for nuclear localization. The targeting sequence was narrowed to amino acids 120 to 129, including a required 126KRK. Although full-length methyltransferase (positions 1 to 476) contains the predicted nuclear localization signals 57RKRK, 80KKRK, 103KKRKR, and 194KKKR, mutagenesis studies confirmed functional motifs only at positions 80, 103, and the previously unrecognized 126KRK. All three motifs can act as alternative nu clear targeting signals. Expression of N-truncated cap methyltransferase (120 to 476) restored viability of methyltransferase siRNA knocked-down cells. However, an enzymatically active 144-476 truncation mutant missing the three nuclear localization signals was mostly cytoplasmic and ineffective in preventing siRNA-induced loss of viability.

Active Transport, Cell Nucleus↗
PubMed2003

Local and systemic control in Ewing's sarcoma of the femur treated with chemotherapy, and locally by radiotherapy and/or surgery.

The role of radiotherapy and/or surgery in the local treatment of Ewing's sarcoma has still to be determined. The outcome of Ewing's sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing's sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone. At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour. The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively. Our results indicate that in patients with Ewing's sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival.

Adolescent↗
PubMed1993

[The local relapse of prostatic cancer and initial local treatment].

We treated fifty cases of prostatic cancer that had no distant metastasis and no other primary cancers between October 1983 and September 1990. Our initial treatment for clinical stages A2, B1, B2 included radical prostatectomy, pelvic lymphadenectomy, and bilateral orchiectomy. Staging lymphadenectomy with bilateral orchiectomy was applied to patients with clinical stage C tumor, and if there was no lymph node metastasis, external beam radiation therapy for the prostate was performed. Patients who did not consent to major surgeries or had poor general status or had clinical stage D1 tumor underwent bilateral orchiectomy. Mean observation period was forty-one months. Eleven cases relapsed. Of the eleven cases, ten had local relapse at the diagnosis of relapse (two of them had distant metastasis simultaneously, six of them had distant metastasis later, and two of them had no distant metastasis in the observation period). All these ten cases had no underwent the initial local treatment. The remainder who had underwent radical prostatectomy relapsed with distant metastasis alone. This study suggests that the local relapse tends to precede distant metastasis as the mate of relapse of prostatic cancer excluding stage D2. There is a possibility that initial local treatment is useful improving the prognosis of the patients for clinical stage A2-D1 prostatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

The local anesthetic activity of tetrodotoxin alone and in combination with vasoconstrictors and local anesthetics.

Tetrodotoxin (TTX), alone and in combination with various vasoconstrictors and local anesthetics, was evaluated for its ability to produce peripheral nerve blocks in the rat and central neural blocks in the cat and dog. High frequency and long duration of block can be attained if sufficiently high concentrations of TTX are used, although latency is long and high dosage may produce systemic toxicity. Frequency and mean duration of block can be increased and systemic toxicity reduced if TTX is administered with a vasoconstrictive agent. Conventional local anesthetics also enhance the nerve-blocking activity of TTX. When appropriate concentrations of TTX and local anesthetics are used, a high frequency of blocks characterized by short latency and long duration can be demonstrated. The studies present some indirect evidence that local anesthetics enhance TTX activity by reversibly increasing the permeability of various neural barriers to TTX.

Anesthesia, Epidural↗
PubMed1992

Influence of local anaesthesia and local hypothermia on leucocyte, temperature, and transferrin response to surgery.

Leucocyte counts, rectal temperature, P-cortisol, P-glucose, P-transferrin, P-orosomucoid, P-IgM and hematocrit were investigated in 24 men undergoing inguinal herniotomy. The patients were randomised to epidural analgesia (n = 8), local infiltration anaesthesia (n = 8) or local infiltration anaesthesia plus local wound hypothermia with ice bags (n = 8). The rectal temperature rose (p less than 0.01) in patients randomised to epidural analgesia but not in the other groups. However, blood granulocyte and acute phase protein changes were similar in all groups. The neural blockade was sufficient in all patients as judged by lack of increase in P-cortisol and P-glucose. Thus, local infiltration anaesthesia and wound hypothermia could not prevent the inflammatory response to small clean surgery.

Adult↗
PubMed1989

[Local anesthetic level and cardiovascular changes following local anesthesia in cataract operations with 3% mepivacaine].

Are there toxic plasma levels of mepivacaine after local anesthesia for ophthalmic surgery with 3% mepivacaine? What hemodynamic changes occur during injection of the local anesthetics? Fifteen patients undergoing cataract surgery were given 10 ml of mepivacaine (3%) as a local anesthetic regardless of body weight. After inserting an arterial line, blood samples were taken before the beginning of the injection of mepivacaine and after 3, 5, 10, 15, 30, and 60 min. Concentrations of the drug were measured by gas chromatography. During the first 15 min arterial blood pressure and ECG were registered continuously on a multichannel recorder. The maximum mepivacaine plasma levels were estimated after 15 min with a range from 0.28 to 6.95 micrograms/ml (means +/- SD: 4.5 +/- 1.47 micrograms/ml). The blood pressure was elevated over the preoperative value, at the beginning of the evaluation period, but there was no change in the blood-pressure level over the whole period. In 4 patients without known cardiac arrhythmias, ventricular or supraventricular extrasystoles occurred. The mepivacaine plasma levels complied with resorption kinetics, which is an indication that there were few intravascular injections and that the injection technique war correct. On the other hand, in some patients the mepivacaine plasma levels exceeded the toxic level. Even in ophthalmic surgery, local anesthetics should be given in relation to the body weight of the patients. The high blood-pressure levels indicated non-optimal preoperative treatment of the hypertonic patients, which was followed by an intraoperative exacerbation of the blood pressure.

Aged↗
PubMed1994

Local recurrence after complete resection for non-small-cell carcinoma of the lung. Significance of local control by radiation treatment.

Of 471 patients undergoing a complete resection for non-small-cell carcinoma of the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with bronchial stump, and 2 with chest wall recurrence) from the 40 patients and assessed the significance of local control by radiotherapy. The median length of survival after disease recurrence for these 32 patients was 19 months. Of 29 patients given radiation treatment, 16 who responded to the treatment survived significantly longer than nonresponders (median survival time 27 months versus 6 months, p < 0.01). Univariate analyses of survival after recurrences in relation to various factors revealed that sex and disease-free intervals were significant prognostic factors (p < 0.05) other than the effect of radiotherapy. A multivariate analysis showed that the effect of radiotherapy was the predominant prognostic factor. From these results, we conclude that local control with radiation is beneficial in patients with solely locally recurrent tumors in terms of improved survival.

Adult↗
PubMed1992

Metabolic responses to oral surgery under local anesthesia and sedation with intravenous midazolam: the effects of two different local anesthetics.

The effects of epinephrine-free and epinephrine-containing local anesthetic solutions on plasma potassium and blood glucose concentrations were investigated in 20 patients undergoing oral surgery with intravenous midazolam sedation. Ten patients were randomly assigned to receive 4.4 mL of 2% lidocaine with 1:80,000 epinephrine as a local anesthetic and 10 were given 4.4 mL of 3% prilocaine with 0.03 IU/mL felypressin. There were significant changes from baseline potassium and glucose concentrations both within and between treatments in the early postinjection period. The epinephrine-containing local anesthetic significantly reduced the plasma potassium concentration 10 min after injection, by 0.16 +/- 0.20 mmol/L (mean +/- SD), and increased the blood glucose concentration at 10, 20, and 30 min (by 0.46 +/- 0.37, 0.63 +/- 0.45, and 0.56 +/- 0.28 mmol/L, respectively). Conversely, plasma potassium increased and blood glucose decreased 10, 20, and 30 min following the administration of the epinephrine-free solution. At 30 min potassium was increased by 0.24 +/- 0.16 mmol/L, and glucose was decreased by 0.23 +/- 0.16 mmol/L. It is concluded that epinephrine-free and epinephrine-containing local anesthetics differ in their metabolic effects during oral surgery with midazolam sedation.

Adult↗
PubMedDate not supplied

Alkalinization of local anesthetics. Which block, which local anesthetic?

BACKGROUND AND OBJECTIVES: A number of clinical studies have been performed in an attempt to establish the effects of alkalinization on potency of local anesthetics. Conflicting results were obtained probably because different studies used different methods as well as different definitions of the effects. To determine the efficacy of alkalinization using different local anesthetic solutions and different regional blocks, 180 patients were studied in a randomized, double-blind fashion. The local anesthetic solutions studied were bupivacaine, mepivacaine, and lidocaine; the regional blocks studied were epidural block, axillary brachial plexus block, and femoral and sciatic nerve block. MATERIALS AND METHODS: In this study, 180 patients receiving epidural block (n = 60), sciatic and femoral nerve block (n = 60), and brachial plexus block (n = 60) were randomized to receive, in a double-blind fashion, a plain or a pH-adjusted solution of 2% mepivacaine, 2% lidocaine, or 0.5% bupivacaine. Onset of sensory analgesia, onset of maximum effect (peak effect or complete analgesia), duration of the block, onset, duration and density of motor block were evaluated using pinprick (Hollmen scale) and a 10-point decimal scale (Seow scale). RESULTS: concerning epidural block, the alkalinization of the local anesthetic shortened significantly the onset of sensory analgesia in the dermatome corresponding to the lumbar interspace used for epidural puncture (L3-L4) and increased the spread of the epidural block in all the groups. The onset of sensory analgesia at L4 level ranged from 10 minutes for plain bupivacaine to 3 minutes for alkalinized lidocaine, whereas the onset at T10 level ranged from 16 minutes for plain bupivacaine and mepivacaine to 12.3 minutes for alkalinized lidocaine. The effects of alkalinization were more evident with lidocaine and bupivacaine. Concerning femoral and sciatic nerve blocks, a statistically significant shorter onset of sensory analgesia and motor block were observed with mepivacaine. Concerning brachial plexus axillary block, the effects of alkalinization were more evident with lidocaine. CONCLUSIONS: Alkalinization produced the best results with lidocaine and bupivacaine for epidural block, with lidocaine for brachial plexus block, and with mepivacaine for sciatic and femoral nerve blocks.

Adult↗
PubMedDate not supplied

[Local recurrence after preoperative irradiation and radical surgery in patients with locally advanced breast carcinoma (clinical stage A)].

The rationale preoperative irradiation is expressed by the sound: eradication of sensitive tumour cells at the periphery of a lesion making complete resection more likely and dissemination of tumour cells by operative manipulation less likely. The dose of irradiation required is approximately 80 to 85% of the dose needed to permanently control the palpable disease, a dose which does not interfere with subsequent mastectomy, if 3 to 4 weeks elapse between the termination of irradiation and mastectomy. One hundred fifteen consecutively examined patients with stage IIIa breast cancer were treated over the period from January 1985 to December 1987 at the Institute of Oncology and Radiology, Belgrade, Serbia. We were interested in the local control of preoperatively irradiated and radically operated patients with the median follow-up of 82 months. Fifteen patients had local recidives, the local control was made in 87%, in the interval between 6 and 66 months (median 18 months). We analyzed the correlation between the local control and the grade of malignancy (GM) of the axillary lymph node and the T status of the tumour. GM was more important than T. Based on our results and on those of other authors, we believe that this multimodal regimen, which includes preoperative irradiation, radical mastectomy and adjuvant cheme-hormonotherapy, is satisfactory for patients with stage IIIa primary breast cancer.

Adult↗