Leuprolide in the treatment of endometrial cancer.
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Aged↗
Biomedical subjects
K Webster
Publications and source records attributed to K Webster.
Low-dose intravenous ondansetron (8 mg) plus dexamethasone: an effective regimen for the control of carboplatin-induced emesis.
Twenty-nine patients with gynecologic malignancies were treated with a fixed low dose of intravenous ondansetron (8 mg) plus dexamethasone (20 mg) in an effort to develop an effective and less expensive antiemetic regimen for the control of carboplatin-induced emesis. Twenty-six (90%) of the women participating in this trial experienced complete control of both acute nausea and vomiting (developing within the first 24 h after chemotherapy administration), while 27 (93%) patients exhibited either complete or major control (< or = 2 episodes of vomiting, < or = 5 episodes of retching, minimal interference with eating) of emesis. On the basis of our experience in this trial, we conclude that the combination of low dose (8 mg) intravenous ondansetron plus dexamethasone is a well-tolerated and highly cost-effective antiemetic strategy for individuals receiving carboplatin-based chemotherapy.
Adult↗
Early results using a porcine dermal collagen implant as an interpositional barrier to prevent recurrent Frey's syndrome.
Frey's syndrome is a common complication of salivary gland surgery. Although it is usually preventable by raising the skin flap in the superficial musculoaponeurotic system layer, the treatment of the established condition often requires further surgery. There are many surgical options to treat this condition. The method described in this paper avoids the morbidity of a second operative site by using a biocompatible interpositional layer to prevent the sweat glands of the skin being inappropriately cross-innervated. The follow-up period on both patients was 12 months. This factor needs to be taken into account despite the early improvement observed.
Adenoma, Pleomorphic↗
Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system.
This paper reports the development and validation of a questionnaire assessing fatigue and anemia-related concerns in people with cancer. Using the 28-item Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire as a base, 20 additional questions related to the symptoms and concerns of patients with anemia were developed. Thirteen of these 20 questions dealt with fatigue, while the remaining 7 covered other concerns related to anemia. Using semi-structured interviews with 14 anemic oncology patients and 5 oncology experts, two instruments were produced: The FACT-Fatigue (FACT-F), consisting of the FACT-G plus 13 fatigue items, and the FACT-Anemia (FACT-An), consisting of the FACT-F plus 7 nonfatigue items. These measures were, in turn, tested on a second sample of 50 cancer patients with hemoglobin levels ranging from 7 to 15.9 g/dL. The 41-item FACT-F and the 48 item FACT-An scores were found to be stable (test-retest r = 0.87 for both) and internally consistent (coefficient alpha range = 0.95-0.96). The symptom-specific subscales also showed good stability (test-retest r range = 0.84-0.90), and the Fatigue subscale showed strong internal consistency (coefficient alpha range = 0.93-0.95). Internal consistency of the miscellaneous nonfatigue items was lower but acceptable (alpha range = 0.59-0.70), particularly in light of their strong relationship to patient-rated performance status and hemoglobin level. Convergent and discriminant validity testing revealed a significant positive relationship with other known measures of fatigue, a significant negative relationship with vigor, and a predicted lack of relationship with social desirability. The total scores of both scales differentiated patients by hemoglobin level (p < 0.05) and patient-rated performance status (p < 0.0001). The 13-item Fatigue subscale of the FACT-F and the 7 nonfatigue items of the FACT-An also differentiated patients by hemoglobin level (p < 0.05) and patient-rated performance status (p < or = 0.001). The FACT-F and FACT-An are useful measures of quality of life in cancer treatment, adding more focus to the problems of fatigue and anemia. The Fatigue Subscale may also stand alone as a very brief, but reliable and valid measure of fatigue.
Adult↗
Lysosomal proteolysis in distally or proximally denervated rat soleus muscle.
We examined the mechanism of accelerated proteolysis in denervated rat soleus muscles. The soleus was denervated by severing either the tibial nerve (proximal, short stump) or sciatic nerve (distal, long stump) at 24, 48, 72, or 96 h before excision. Twenty-four hours after denervation, the extent of atrophy was similar for proximal and distal denervation, although lysosomal latency declined in both groups. After 48 and 72 h, denervation resulted in a decline in protein content, an increase in in vitro protein degradation, and a decline in lysosomal latency, all of which were greater in proximally denervated than in contralateral distally denervated muscles. These differences between acute responses of proximally and distally denervated muscles suggest the retention of some factor in the longer nerve stump that attenuates atrophy. After 96 h, total protein loss, protein degradation, and lysosomal latency were similar for proximal and distal denervation, suggesting the loss of axoplasmic flow from the long nerve stump.
Animals↗
Effects of inspiratory muscle unloading on the response of respiratory motor output to CO2.
Inspiratory muscle output is downregulated when the mechanical load is reduced in awake humans. It is not known whether this is related to reduction in PCO2 or to removal of load-related neural responses. To address this issue, we did Read CO2 rebreathing tests in 13 normal subjects with and without unloading and compared respiratory output at identical end-tidal PCO2 (PET(CO2)) levels. Unloading was carried out with proportional assist ventilation (flow assist = 2 cm H2O/L/s plus volume assist = 4 cm H2O/L, representing approximately 50% reduction of the normal resistance and elastance). Ventilatory output (n = 13), total pressure of respiratory muscles (Pmus, n = 8), and transdiaphragmatic pressure (Pdi, n = 5) were computed at different PET(CO2) levels. Pmus was computed from esophageal pressure (Pes) using the Campbell diagram, and Pdi was measured from the difference between gastric pressure and Pes. Unloading caused an increase in ventilation (VI) and tidal volume (VT) at all PET(CO2) levels with no significant effect on slope (VI/PET(CO2) or VT/PET(CO2)) or respiratory rate. At low PET(CO2) (50 mm Hg), Pdi and Pmus waveforms did not differ with and without unloading. At high PET(C02) (59 mm Hg), peak Pdi and Pmus decreased by only 18.8 +/- 8.3% and 13.8 +/- 9.5%, respectively (NS, p > 0.05). Using a model that allows nonlinearity in the pressure-volume relation and for intrinsic muscle properties (force-length and force-velocity relations), we estimated the expected changes in mean VT and VI when the level of assist used in this study was applied in the absence of any change in neural output response to CO2. The predicted and observed changes in VT and VI were similar. We conclude that when chemical stimuli are rigorously controlled, unloading does not result in downregulation of respiratory muscle activation.
Adult↗
Respiratory response to CO2 during pressure-support ventilation in conscious normal humans.
The respiratory response to CO2 during pressure-support ventilation (PSV) was studied in 16 conscious normal humans. The subjects breathed through a mouthpiece connected to a ventilator in PSV mode, with pressure set to the highest comfortable level for each subject (10.1 +/- 0.6 cm H2O, mean +/- SE). Compared with breathing spontaneously through the ventilator (CPAP mode with zero positive end-expiratory pressure), with PSV, tidal volume (VT) increased significantly (1.16 +/- 0.1 versus 0.85 +/- 0.04 L), whereas breathing frequency (f) remained stable (16.0 +/- 0.9 versus 15.6 +/- 1.1 breaths/min). As a result, the subjects hyperventilated, decreasing significantly end-tidal PCO2 (PETCO2, 23.5 +/- 1.2 versus 35.5 +/- 1.1 mm Hg). Fraction of inspired CO2 (FICO2) was then increased in steps, and changes in respiratory motor output were quantitated from changes in f, VT, ventilation (VI), peak inspiratory flow (Vpeak), and muscle pressure (Pmus). Pmus was calculated by the equation of motion, based on respiratory system mechanics, which were measured previously by airway occlusion at end-inspiration, VT, VI, and Pmus increased significantly with increasing PETCO2, and the response was detectable even below eupneic levels; f remained relatively stable over a wide range of PETCO2 (23 to 45 mm Hg) and increase significantly only when PETCO2 approached 50 mm Hg. These results indicate that in conscious normal humans during PSV, CO2 responsiveness extends well into hypocapnia and is expressed principally as an increase in intensity of respiratory motor output with little change in respiratory rate.
Adult↗
Simplified regimen for the prevention of paclitaxel-associated hypersensitivity reactions.
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Dexamethasone↗
Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience.
To examine the toxicity profile and antineoplastic activity of carboplatin (area under the concentration-time curve of 4 to 7.5) plus 3-hour infusional paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 or 175 mg/m2) in women with advanced gynecologic malignancies, we retrospectively reviewed the experience of the Gynecologic Cancer Program at The Cleveland Clinic with this combination chemotherapy regimen. To date, 92 patients (median age, 67 years) have received a total of 460 courses (median number per patient, six) of this two-drug combination. The initial paclitaxel dose was 175 mg/m2 and the carboplatin area under the concentration-time curve was > or = 5 in 72% and 73% of patients, respectively. The major toxicity was neutropenia (grade 4 in 9% of patients), resulting in two febrile episodes and a single septic death. Grade 4 thrombocytopenia and grade 3 peripheral neuropathy were noted in one and two patients, respectively. Twelve patients (13%) experienced at least one episode of paclitaxel-associated hypersensitivity, but all were able to continue with the treatment program. Of the 62 patients with ovarian cancer or primary peritoneal carcinoma with carbohydrate antigen-125 levels > or = 60 U/mL before the initiation of chemotherapy, 74% exhibited a > or = 90% decline in the tumor marker following treatment. We conclude that the combination of carboplatin and 3-hour infusional paclitaxel can be administered in the outpatient setting with a highly acceptable toxicity profile and with major activity in patients with ovarian cancer and primary carcinoma of the peritoneum.
Adult↗
Serum CA-125 measurements > 65 U/mL. Clinical value.
OBJECTIVE: To review the prevalence of various conditions associated with serum CA-125 values > 65 U/mL, to calculate the odds ratios of different ranges of high CA-125 in predicting cancer and to study the effect of menopause and the presence of a mass on the predictive value of high serum CA-125. STUDY DESIGN: A retrospective review of the diagnoses in 313 consecutive women seen at the Cleveland Clinic Foundation whose serum CA-125 was > 65 U/mL was performed. Statistical analysis was performed using crosstabulation, chi 2, Fisher's exact test and the odds ratio. RESULTS: In patients with serum CA-125 > 65 U/mL, gynecologic cancers, nongynecologic cancers and non-malignant conditions constituted 74.3%, 10.2% and 13.1% of diagnoses, respectively. In patients with serum CA-125 > or = 1,000 U/mL, the same conditions were responsible for 89%, 7% and 3% of diagnoses, respectively. Endometriosis and metastatic breast cancer were the most common benign condition and nongynecologic cancer associated with serum CA-125 > 65 U/mL. The presence of an abdominopelvic mass significantly increased the risk of malignancy (P < .00005). Approximately 90% of patients with CA-125 > 65 U/mL and no mass had nonmalignant disease. The diagnoses of serum CA-125 values > 65 U/mL varied significantly in premenopausal versus postmenopausal patients. Postmenopausal patients had a higher incidence of gynecologic (P = .002) and nongynecologic (P = .0008) cancers and lower incidence of benign conditions (P < .0005). The odds ratio that CA-125 levels were associated with cancer increased as the level of CA-125 increased. The odds ratio of malignant versus benign disease was significantly higher in post-menopausal patients for all intervals of CA-125 levels until the level of > or = 1,000 U/mL was reached. CONCLUSION: In patients seen at a tertiary center, serum CA-125 measurements > 65 U/mL were associated with nonmalignant conditions in 13% of patients. Although higher serum CA-125 levels were more associated with gynecologic malignancies, no level of CA-125 occurred exclusively with gynecologic cancers. In postmenopausal patients with serum CA-125 values > 65 U/mL and in patients with serum CA-125 values > 65 U/mL and an abdominopelvic mass, subspecialty consultation should be considered before proceeding to surgery.
Adult↗
Linking outcomes management to quality-of-life measurement.
Health-care workers now accept quality of life (QOL) as an important outcome to evaluate in clinical research and as a useful measure of quality care. Indeed, current demand for QOL assessment in clinical practice has outpaced the availability of valid, streamlined, cost-effective methods for carrying out such assessment, although new tools are in the offing. This paper will highlight some of the major challenges facing outcomes management and outcomes research, with particular focus on the development of a QOL instrument to evaluate and manage anemia and fatigue in cancer patients--the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The newest version of broader QOL assessment system, the Functional Assessment of Chronic Illness Therapy (FACIT), will also be described.
Cohort Studies↗
Epidemiology of hypodermosis in Spain: benefits of serology over clinical examination.
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Animals↗
Control of carboplatin-induced emesis with a fixed low dose of granisetron (0.5 mg) plus dexamethasone.
In an effort to develop a cost-effective antiemetic regimen for carboplatin-based chemotherapy, we examined a fixed (0.5 mg) low dose of granisetron (a new 5-HT3 (serotonin) antagonist) plus dexamethasone (20 mg) in 23 patients with gynecologic malignancies receiving this antineoplastic drug. Nineteen (83%) patients experienced complete control of acute emesis (nausea and vomiting) while 22 (96%) individuals demonstrated complete or major control (< or = 2 episodes of vomiting, < or = 5 episodes of retching, minimal interference with eating) of emetic events. We conclude that this fixed low-dose granisetron plus dexamethasone regimen is a safe, convenient, and cost-effective antiemetic program for individuals receiving carboplatin-based chemotherapy.
Adult↗
Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with gynecologic cancers: unexpected incidence of neurotoxicity.
In an effort to develop a paclitaxel plus cisplatin combination chemotherapy regimen which can be easily employed in the outpatient setting, 38 patients (median age, 59; range, 39-72) with gynecological malignancies (20 ovarian; 6 primary peritoneal; 12 endometrial) seen at the Cleveland Clinic Foundation from June 1993 to May 1995 were administered 170 cycles of paclitaxel (135 or 175 mg/m2) over 3 hr followed by cisplatin (starting dose 75 mg/ m2). Of the 33 patients with elevated CA-125 levels prior to the initiation of chemotherapy, all experienced > 50% decreases in this antigen level, while 23/33 (70%) had > 90% reductions. In general, nonneurologic side effects were mild in severity and easily manageable. Unfortunately, 71% of the patients developed neurologic toxicity, with one-fifth of the treated population experiencing severe neurotoxic side effects (grade 3-4). We conclude that paclitaxel administered over 3 hr at a dose of 135 or 175 mg/m2, followed by cisplatin (75 mg/m2), is a highly active regimen in gynecologic malignancies. Unfortunately, in our experience, the incidence and severity of neurotoxicity with this regimen is considerably greater than that reported with paclitaxel administered over 24 hr in combination with cisplatin. As a result of the observed toxicity profile, this drug delivery schedule for cisplatin and paclitaxel cannot be recommended for general clinical use.
Adult↗
Response of ventilator-dependent patients to different levels of proportional assist.
Proportional-assist ventilation (PAV) is a form of ventilatory support in which airway pressure increases in proportion to patient effort. Because it effectively reduces the mechanical load to an adjustable extent, PAV permits the study of the pattern of breathing in patients with respiratory disease when unconstrained by abnormal respiratory mechanics. We studied 11 patients with assorted medical problems requiring ventilatory support. The patients were switched to PAV, and the level of support was varied from near-maximal levels to the lowest tolerable level. Each level was maintained for several minutes while ventilation (VE), tidal volume (VT), and respiratory rate (f) were monitored. The breathing pattern observed with the highest assist varied substantially among patients. The ranges (and means) of VE, VT, and f were 5.6-18.7 (12.8) l/min, 203-844 (517) ml, and 18-33 (25) breaths/min, respectively. The correlation between VT and VE at the highest assist was very high (r = 0.91), suggesting that ventilatory demand is the most important determinant of VT variability. There were no systematic changes in breathing pattern as the level of assist was altered; at the highest and lowest levels of support, VE, VT, and f were, respectively, 12.8 +/- 5.4 (SD) vs. 11.6 +/- 4.3 l/min, 517 +/- 217 vs. 459 +/- 175 ml, and 25.0 +/- 4.2 vs. 25.7 +/- 3.9 breaths/min. These results indicate that within each patient, in a given state, there exist unique values for a desired VE, VT, and f that are largely independent of the mechanical load; if assist is increased, patient effort is decreased to maintain the desired ventilatory targets.
Adult↗
Respiratory control during volume-cycled ventilation in normal humans.
The purpose of this study was to evaluate the extent of inhibition to respiratory rhythm associated with high volumes of ventilation during volume-cycled mechanical ventilation (neuromechanical inhibition). Two approaches were used. 1) In 18 normal awake subjects, ventilator tidal volume (VT) in the assist/control mode (A/C) was increased in steps from the minimum tolerable level up to 80% of the subject's inspiratory capacity or ventilator's maximum VT. We looked for appearance of intermittent apnea or a reduction in spontaneous rate (f). 2) Another 18 normal awake subjects were placed on controlled mechanical ventilation (CMV). When apnea was established, we abruptly terminated CMV and measured the time before the appearance of the next spontaneous effort. In the assist mode (protocol 1), we did not observe intermittent apnea because VT was increased from [from 944 +/- 198 to 1,867 +/- 277 (SD) ml], and there was only a modest reduction in f (14.1 +/- 3.9 to 12.4 +/- 4.0 breaths/min). End-tidal PCO2 (PETCO2) decreased precipitously as VT was increased. In protocol 2, we did not observe apnea after discontinuation of CMV in any subject. Total breath duration of the first breath after discontinuation did not differ significantly from total breath duration during A/C in the same subjects (4.84 +/- 2.2 vs. 5.2 +/- 2.0 s). This similarly applied regardless of route of breathing (nose vs. mouth) or PETCO2 level at time of discontinuation. We conclude that neuromechanical inhibition is quite weak and provides very little negative feedback that may help control PCO2 in the face of excessive VT and f demands of the subject.
Adult↗
Effects of breathing route, temperature and volume of inspired gas, and airway anesthesia on the response of respiratory output to varying inspiratory flow.
The determinants of the response of the respiratory output to inspiratory flow rates (VI) were examined in awake normal subjects. Subjects were connected to a volume-cycle ventilator in the assist/control mode, and VI was increased in steps from 30 to 90 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered. In six subjects the effects of breathing route (nasal or mouth) and temperature and volume of inspired gas (Protocol A) and in 8 subjects the effects of airway anesthesia (upper and lower airways; Protocol B) on the response of respiratory output to varying VI were studied. In Protocol B, in order to calculate muscle pressure during inspiration (Pmus), respiratory system mechanics were measured using the interrupter method at end-inspiration. Independent of conditions studied, breathing frequency increased significantly and end-tidal concentration of CO2 decreased as VI increased. The response was graded and reversible and not affected by breathing route, temperature and volume of inspired gas, and airway anesthesia. With and without airway anesthesia (Protocol B), neural inspiratory and expiratory time and neural duty cycle, estimated from Pmus waveform, decreased significantly as VI increased. At all conditions studied, the rate of change in airway pressure prior to triggering the ventilator tended to increase as VI increased. The changes in timing and drive were nearly complete within the first two breaths after transition, with no evidence of adaptation during a given VI period. We conclude that VI exerts an excitatory effect on respiratory output which is independent of breathing route, temperature and volume of inspirate, and airway anesthesia. The response most likely is neural in origin, mediated through receptors not accessible to anesthesia, such as those located in the chest wall or below the airway mucosa.
Adult↗
Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure.
We evaluated the efficacy of noninvasive mechanical ventilation (NIMV) in alleviating distress and avoiding intubation in patients with de novo acute respiratory failure complicating primary medical disorders. Eleven consecutive patients with severe respiratory distress were entered. In all patients a decision to intubate on an urgent basis had been made, but NIMV could be initiated within minutes. The patients suffered from acute pulmonary edema (five), sepsis/ARDS (two), status asthmaticus (two), and severe pneumonia (two). Dyspnea score (max=10) was (+/- SD) 8.4 +.- 1.6, scale for accessory muscle use (max=5) was 4.2 +/- 0.7, and respiratory rate was 37.6 +/- 3.8 min -1. Pa CO2, pH, and base excess (BE) were 48 +/- 18 mm Hg, 7.27 +/- 0.13, and -5.5 +/- 7.4, respectively, with five patients showing severe metabolic acidosis (BE < - 10). NIMV was applied using proportional assist ventilation. There were three early failures. These included the two patients with sepsis/ARDS who did not tolerate the mask. One patient failed because Pa CO2 and pH deteriorated despite subjective improvement. The remaining eight patients demonstrated progressive improvement, and none required intubation. The duration of NIMV was 3 h to 2 d. We conclude that when NIMV is made available on a "few minutes" basis, selected patients with severe de novo respiratory distress/failure caused by reversible medical disorders, who would otherwise have been intubated, can be given substantial relief and be spared intubation.
Acid-Base Imbalance↗