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PubMed1998

Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor hypoxia and tumor cell repopulation are known factors determining radiation response. Accelerated radiotherapy as a method to counteract cellular repopulation was combined with carbogen (95% O2 + 5% CO2) breathing and oral administration of nicotinamide as a means to improve tumor perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness of this approach as a voice-preserving treatment for carcinoma of the larynx was assessed in a prospective study. PATIENTS AND METHODS: Sixty-two patients with stage III-IV laryngeal carcinoma were treated with a schedule of accelerated radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days. Radiotherapy was combined with carbogen breathing in the initial 11 patients and with both carbogen and nicotinamide administration in the subsequent 51 patients. RESULTS: After a median follow-up of 24 months, the actuarial local control rate at 2 years was 92%. This is higher than any previous report in the literature for this category of patients. Five patients had a local tumor recurrence and underwent laryngectomy. There was one regional recurrence. Including salvage surgery the loco-regional control rate was 100%. Four patients developed distant metastases and died. The actuarial overall survival rate at 2 years was 85%. Toxicity was increased relative to conventional radiotherapy but was considered as acceptable. One patient underwent laryngectomy for radiation-induced cartilage necrosis. CONCLUSION: These preliminary results indicate that advanced laryngeal cancer can be controlled in a high proportion of patients when treated with accelerated radiotherapy combined with carbogen and nicotinamide. This approach offers excellent possibilities for larynx preservation.

Actuarial Analysis↗

PubMed2002

Rapid acceleration of the lower arm correlates with agonist EMGs during the initial phase.

Fifty-eight healthy subjects made rapid elbow extensions to a target over 54 degrees. Angular acceleration was measured and surface electromyograms (EMGs) were recorded from the antagonistic muscles using monopolar rather than bipolar electrode configurations. Marked individual differences were found in the peak value of the first derivative of acceleration (dAcc/dt_Pk). The dAcc/dt_Pk correlated with both quantitative and qualitative properties of the agonist EMGs, but not with those of the antagonist EMG. The agonist EMGs, integrated until the moment of dAcc/dt_Pk, were positively correlated with dAcc/dt_Pk. The interval between EMG onset and EMG peak decreased with increasing dAcc/dt_Pk. The duration of the initial negative phase in the EMGs, which was considered to index the time required to recruit high-threshold MUs, decreased with increasing dAcc/dt_Pk. The results indicate that the ability to rapidly accelerate the lower arm varies across subjects, probably due in part to individual differences in the neural capacity to drive the agonists.

Adolescent↗

PubMed2002

Accelerated hyperfractionated radiation, concurrent paclitaxel/cisplatin chemotherapy and surgery for stage III non-small cell lung cancer.

The low surgical cure rate in patients with stage III non-small cell lung cancer has prompted an exploration of multimodality treatment strategies. Mature results are presented from a phase II trial of accelerated hyperfractionated radiation therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage III non-small cell lung cancer underwent induction treatment with a 96 h continuous cisplatin infusion (20 mg/m(2) per day) and a 24 h infusion of paclitaxel (175 mg/m(2)) given concurrently with accelerated hyperfractionated radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was completed in ten treatment (12 total) days. Surgical resection was scheduled 4 weeks later with a second identical course of chemoradiotherapy given 4-6 weeks post-operatively, to a total radiation dose of 60-63 Gy. Thirty-five patients had stage III(A) disease and ten had stage III(B) disease (eight with N(3) tumors). Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia <1000/mm(3) in 84% which required hospitalization for fever in 40%. There were no toxic deaths during induction. About 40 of the 45 patients (89%) were operable and 32 (71%) were resectable for cure. A pathologic response was identified in 22 patients (49%); five patients (11%) had no residual disease. Fourteen patients (31%) were downstaged to mediastinal node negativity. With a median follow-up of 60 months, the Kaplan-Meier projected 5-year overall survival was 29%; locoregional control 79%; and distant metastatic disease control 38%. The projected 5-year survival for the 14 patients downstaged to mediastinal node negativity was 50%. For the 19 patients with residual ipsilateral mediastinal node involvement at surgery it was 32%. This short-course of paclitaxel and cisplatin chemotherapy and concurrent accelerated fractionation radiation is tolerable despite significant myelosuppression. Locoregional control is excellent and survival is better than historical expectations. Patients downstaged to mediastinal node negativity have a prognosis similar to those with de novo stage I(B) and II disease. Distant metastases are the major cause of treatment failure.

Adult↗

PubMed2000

Estimating a treatment effect with the accelerated hazards models.

In randomized clinical trials, when the outcome of interest is time to event, the proportional hazards model or the accelerated failure time model is often used to identify a treatment effect. In this article, we discuss a simple alternative called the accelerated hazards model in which the treatment effect is characterized as the hazard progression time ratio, when the treatment is believed to accelerate or decelerate the underlying hazard progression through time. Survival data from an actual randomized placebo-controlled trial, which evaluates the effectiveness of biodegradable polymers with carmustine to treat malignant gliomas, is used for illustration.

Antineoplastic Agents, Alkylating↗

PubMedDate not supplied

Accumulation of proteolytic fragments of mutant presenilin 1 and accelerated amyloid deposition are co-regulated in transgenic mice.

The activities of presenilin 1 (PS1) and 2 modulate the proteolytic processing of amyloid precursor proteins to produce Abeta1-42, and mutations in these proteins are associated with an accelerated rate of Abeta deposition. PS1 and PS2 themselves are subject to a highly-regulated endoproteolytic cleavage to generate stable 27 kDa N-terminal and 17 kDa C-terminal fragments. Here, we examined the relationship between the regulated cleavage of PS1 and the acceleration of Abeta deposition in transgenic mice that co-express Mo/Hu APPswe and varied levels mutant PS1 (A246E variant). The steady-state levels of the N- and C-terminal fragments of mutant PS1 in mice expressing low levels of mRNA were similar to that of mice expressing high levels of mRNA. Only mice expressing high levels of transgene mRNA accumulated uncleaved full-length protein. In mice co-expressing low levels of PS1A246E mRNA with Mo/Hu APPswe the age of appearance of Abeta deposits was similar to that of mice co-expressing expressing Mo/Hu APPswe with very high levels of mutant PS1. Our findings demonstrate that the levels of accumulated human PS1 N- and C-terminal fragments do not increase in proportion to the level of transgene mRNA and that similarly, the magnitude by which mutant PS1 accelerates the deposition of beta-amyloid is not proportional to the level of transgene expression.

Aging↗

PubMedDate not supplied

Senescence-accelerated mouse (SAM): a biogerontological resource in aging research.

The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) has been under development since 1970 through the selective inbreeding of AKR/J strain mice donated by the Jackson laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. The characteristic feature of aging common to all SAMP and SAMR mice is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains manifest various pathobiological phenotypes which include such neurobiological phenotypes as deficits in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, etc., and are often characteristic enough to differentiate the strains. Various efforts are currently being made using the SAM model to clarify the underlying mechanisms in accelerated senescence as well as the etiopathogenic mechanisms in age-associated pathobiologies. Genetic background and significance of SAM development are discussed.

Aging↗

PubMed2001

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.

PURPOSE: To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). METHODS AND MATERIALS: Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). RESULTS: This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072). CONCLUSION: With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.

Adult↗

PubMed2002

Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer.

PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split-course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy. RESULTS: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors.

Adult↗

PubMed1996

Local control of T3 carcinomas after accelerated fractionation: a look at the "gap".

PURPOSE: To study the effects of midcourse treatment break or gaps related to the local control of T3 carcinoma of the oropharynx and larynx following accelerated hyperfractionated radiation therapy. METHODS AND MATERIALS: All patients were treated at the Massachusetts General Hospital from 1979 through 1994 with treatment consisting of 1.6 Gy per traction, two fractions a day for the treatment of T3 carcinoma of the oropharynx and larynx. They were entered in the head and neck data base. Their treatment dates, treatment breaks, and doses vs. local control were analyzed and compared. A p-value of 0.05 was considered statistically significant. RESULTS: A total of 162 patients were available for review. Due to the acute severe mucosal effects, most of the patients required a midcourse pause or "break" after a dose of 38.4-48 Gy before treatment could be resumed and completed. The data indicate that (a) prolongation of the treatment gap for more than 14 days, (b) total treatment course longer than 45 days, (c) total dose less than 67 Gy, and (d) male gender adversely affected local control. In spite of the gaps, the female patients with advanced carcinomas enjoyed the benefits of improved local control after the accelerated hyperfractionated radiation therapy. CONCLUSIONS: Accelerated hyperfractionation radiation therapy using 1.6 Gy per fraction/twice-a-day (b.i.d.) for a total dose of 70.4 Gy in 6 weeks is effective in achieving high local control of T3 squamous cell carcinoma of the oropharynx and larynx. The midcourse treatment gap should be as short as possible with the projected total dose and time. Should the gaps be unduly prolonged due to various circumstances, further increase in the total dose, for example, 72-75 Gy, and/or increase of the fraction sizes, for example, 1.8-2.0 Gy/f b.i.d. after the gap may be necessary to compensate for the adverse effects of the tumor regeneration from the prolonged gap.

Adolescent↗

PubMed1999

A phase II study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage III non-small-cell lung cancer.

PURPOSE: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplastin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. METHODS AND MATERIALS: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m(2)) was given intravenously on days 1 and 29, and etoposide (50 mg/m(2)) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. RESULTS: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade > or = 3 toxicity. CONCLUSION: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation.

Administration, Oral↗

PubMed1999

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation.

PURPOSE: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. METHODS AND MATERIALS: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. RESULTS: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively. CONCLUSION: Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Adenocarcinoma↗

PubMed1999

Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas?

PURPOSE: To assess the impact of treatment interruption on the potential gain in locoregional control obtained with accelerated radiotherapy (RT) compared with conventionally fractionated RT in patients with oropharyngeal carcinomas. METHODS AND MATERIALS: 152 patients treated with radical RT for oropharyngeal carcinomas between 1979 and 1996 were retrospectively analyzed. According to the American Joint Committee on Cancer (AJCC) staging system, there were 6/30/43/73 stages III/III/IV. Sixty-one patients were treated with a conventional RT schedule (median dose 70 Gy in 35 fractions), and 91 patients with either of two 5/5.5-week accelerated RT schedules (median dose 69.6-69.9 Gy in 41 fractions). Discounting weekends, RT was interrupted for 2 consecutive days or more in 53 patients (median duration 11 days, range 2-97), including 67% of the patients in the conventional RT group and 13% in the accelerated RT group. Median follow-up for surviving patients was 55 months (range 23-230). The Cox proportional hazards model was used for the multivariate analysis of factors influencing locoregional control. RESULTS: In univariate analysis, factors associated with a significant decrease in locoregional control included WHO performance status > or =1, advanced AJCC stages (III and IV), conventional RT fractionation, overall treatment time > or =44 days (median), and RT interruption. In the multivariate analysis, when introduced into the model individually, the three significant therapeutic factors remained significant after adjustment for the forced clinical variables. However, when the three therapeutic factors were introduced together into the model, beside the AJCC stage (P = 0.017), only RT interruption remained a significant independent adverse prognostic factor (P = 0.026). CONCLUSIONS: This multivariate analysis highlights the potential negative impact of treatment gaps on locoregional control in oropharyngeal carcinomas. This suggests that treatment interruption may be an even more important parameter than the type of RT schedule per se. Thus, when assessing the relative merit of two RT schedules, inclusion of the other therapeutic factors in a multivariate model is mandatory in order to avoid misinterpretation of the results.

Adult↗

PubMed2000

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma.

PURPOSE: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m(2), amifostine (Ethyol, U.S. Bioscience) 15-30 min prior to each radiation session. RESULTS: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of "at least Grade 3" mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months. CONCLUSION: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.

Adult↗

PubMed2003

Components of Panax ginseng that improve accelerated small intestinal transit.

We previously clarified that Dai-kenchu-to, a Chinese prescription, was useful for improving carbachol-induced hyperperistalsis of the small intestine in vivo, and the efficacy of Ginseng Radix, a crude drug component of Dai-kenchu-to, was also confirmed. Ginseng Radix, the root of Panax ginseng C.A. Meyer, showed significant ameliorative effects on both the carbachol-induced and the BaCl(2)-induced accelerated small intestinal transit model in mice, suggesting that both an inhibitory effect on the cholinergic nervous system and direct suppressive effect on muscles were involved in the ameliorative effect of Ginseng Radix on the accelerated small intestinal transit. Ginsenoside Rb1 (4) and ginsenoside Rd (7), major components of Ginseng Radix, improved both animal models. These results suggest that ginsenoside Rb1 (4) and ginsenoside Rd (7) were representative compounds of Ginseng Radix for improving the accelerated movement of the small intestine and that these compounds partly contribute to the action of Dai-kenchu-to on small intestinal transit.

Animals↗

PubMed2002

Vertical eye-movement oscillation with a frequency double that of lateral linear acceleration in patients with long-standing unilateral vestibular loss.

OBJECTIVE: To examine our hypothesis that an unusual floating or tilting sensation claimed by patients with long-standing unilateral vestibular loss might be attributed to incomplete central compensation in the otolith system. METHODS: Seven patients who were with or without symptoms for 6-101 months after intratympanic gentamicin therapy for unilateral endolymphatic hydrops were sinusoidally exposed to lateral linear acceleration, and their compensatory eye movements were compared with those of 18 normal controls, using electro-oculography (EOG). The subjects, secured firmly in the chair of a linear accelerator (sled), were oscillated at three different G-loadings of 0.1 (0.11 Hz), 0.2 (0.16 Hz) and 0.3 G (0.19 Hz), respectively. During displacement, they gazed at a real (visible) or imaginary target which was located on the wall (earth-fixed), or moved on the wall in sync with the sled (body-fixed). RESULTS: Vertical EOG (V-EOG) with a frequency two-fold that of the stimulus frequency was characteristically evoked in all patients, but in none of the normal controls. One of the doubled V-EOG was larger in amplitude than the other, when the stimulus acceleration was directed from the affected ear to the intact ear in those patients whose symptoms still remained. Such a directional difference tended to be greater with the imaginary target than with the visible target. In the horizontal EOG, there was no marked difference between the patients and normal controls. Nobody reported tilt perception but only horizontal translation during the sled displacement, except one patient who was examined twice; a roll tilt was perceived in the first examination when she still had symptoms, but no tilt sensation in the second one when she no longer had symptoms. CONCLUSION: It was suggested that incomplete compensation in the otolith system could cause unusual sensations even after long-standing unilateral vestibular loss, and that V-EOG induced by a sled might be helpful in evaluating functional recovery.

Adult↗

PubMed2003

Correlation between accelerated presbycusis and decreased immune functions.

The aim of the current study is to analyze the relationship between presbycusis and the immune system, which is affected by pathogenic environments, and to devise a strategy for the prevention of presbycusis using the SAMP1 mouse, an animal model for accelerated senescence that shows both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells in the cochlea. When these mice were bred in different pathogenic environments, we found that the development of age-related diseases such as presbycusis was delayed in the mice bred under clean conditions. Prednisolone administration showed no significant prevention of the development of presbycusis in the mice, suggesting that autoimmune mechanisms are not involved in the acceleration of presbycusis. It is conceivable that pathogen-induced infections impose a severe stress on the host, impairing the host's immune functions. A reduction in the number of pathogens may therefore prevent the acceleration of the aging process. These findings suggest that not only the gene backgrounds but also immune functions affect the development of presbycusis in SAMP1 mice. Further studies into the relationship between systemic immune functions and the neuro-generation system may provide additional information about the treatment for age-related diseases.

Aging↗

PubMed1992

Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group.

To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Use of exercise Doppler echocardiography to evaluate cardiac drugs: effects of propranolol and verapamil on aortic blood flow velocity and acceleration.

This study evaluated the ability of exercise Doppler echocardiography to identify hemodynamic changes due to cardiac medication. Twenty young healthy volunteers (mean age 30 years) underwent continuous wave Doppler examination from the suprasternal notch at rest, during each stage of a standard exercise protocol and immediately after exercise. On completion of the control test, each subject received either 60 to 80 mg of propranolol or 120 mg of verapamil orally, and the same exercise protocol was repeated after 90 min. During the control test, values for modal velocity, acceleration and flow velocity integral all increased significantly from baseline (p less than 0.0002 for each). When exercise was repeated after propranolol administration, values for all Doppler measurements were significantly altered. Modal velocity at baseline was significantly lower after propranolol when compared with control (0.53 +/- 0.11 versus 0.63 +/- 0.17 m/s; p less than 0.0001). Similarly, modal velocity at maximal exercise was significantly lower after propranolol (1.11 +/- 0.2 versus 1.25 +/- 0.21 m/s; p less than 0.0001). The effect of propranolol on acceleration was even greater, with blunting of baseline (11.4 +/- 2 versus 15.4 +/- 5 m/s per s; p less than 0.0005) and exertional (33.4 +/- 10 versus 56.3 +/- 15 m/s per s; p less than 0.0001) acceleration. The flow velocity integral during exercise was greater after propranolol (14.1 +/- 3.1 versus 10.1 +/- 3.2 cm; p less than 0.0005) than during the control test. Verapamil failed to influence any Doppler-measured index of aortic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗