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Biomedical subjects

K Webster

Publications and source records attributed to K Webster.

At least 37 records · Page 2Linked to original sources
PubMed2000

Experience with prophylactic oral ciprofloxacin in gynecological cancer patients developing severe chemotherapy-induced neutropenia.

The development of significant neutropenia is a relatively frequent complication of cytotoxic chemotherapy of malignant disease. In an effort to develop a cost-effective management strategy to prevent serious infectious events associated with severe chemotherapy-induced neutropenia, patients treated in the Gynecological Oncology Program of the Cleveland Clinic Taussig Cancer Center have been administered ciprofloxacin, a potent broad-spectrum antibiotic, 500 mg orally twice a day, beginning at the time of documentation of grade 4 neutropenia. The antibiotic is continued until granulocyte recovery. A total of 44 patients (57 treatment courses) have been treated in this manner. There have been no complications of therapy and no episodes of subsequent infections due to ciprofloxacin-resistant organisms. Two patients required hospital admission following the development of significant fever, despite the use of ciprofloxacin. While these results are encouraging and suggest that the use of prophylactic ciprofloxacin is a highly cost-effective management approach in this setting, randomized controlled trials are necessary to define the ultimate benefit of this clinical strategy.

Adult↗
PubMed2000

Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis.

To determine whether stretch-induced activation of p53 is necessary for the up-regulation of the local renin-angiotensin system and angiotensin II (Ang II)-induced apoptosis, ventricular myocytes were infected with an adenoviral vector carrying mutated p53, Adp53m, before 12 hours of stretch. Noninfected myocytes and myocytes infected with AdLacZ served as controls. Stretching of Adp53m-infected myocytes prevented stimulation of p53 function that conditioned the expression of p53-dependent genes; quantity of angiotensinogen (Aogen), AT(1), and Bax decreased, whereas Bcl-2 increased. Ang II generation was not enhanced by stretch. Conversely, stretch produced opposite changes in noninfected and AdLacZ-infected myocytes: Aogen increased twofold, AT(1) increased 2. 1-fold, Bax increased 2.5-fold, and Ang II increased 2.4-fold. These responses were coupled with 4.5-fold up-regulation of wild-type p53. Stretch elicited comparable adaptations in p53-independent genes, in the presence or absence of mutated p53; renin increased threefold, angiotensin-converting enzyme increased ninefold, and AT(2) increased 1.7-fold. Infection with Adp53m inhibited myocyte apoptosis after stretch. Conversely, stretch increased apoptosis by 6.2-fold in myocytes with elevated endogenous wild-type p53. Thus, a competitor of p53 function interfered with both stretch-induced Ang II formation and apoptosis, indicating that p53 is a major modulator of myocyte renin-angiotensin system and cell survival after mechanical deformation.

Angiotensin II↗
PubMed2000

The adherence to guidelines for facial radiography in an Accident & Emergency Department.

OBJECTIVES: To evaluate the degree of adherence to guidelines for facial radiography. METHODS: A retrospective review of 1538 facial radiographs from a consecutive series of 414 patients attending the Accident & Emergency Department of the North Staffordshire Hospital with suspected facial injuries over a 6 month period was undertaken. Information on age, sex and aetiology of injury was recorded along with the type of view and total number of films taken. The results were compared with guidelines from the Department of Oral & Maxillofacial Surgery. RESULTS: Almost one-half of all injuries were due to assault. There was general adherence to the guidelines in terms of the number of films taken for mid-face and mandibular fractures. CONCLUSIONS: There was a good adherence to the guidelines in terms of the number of films taken for midface and mandibular fractures. However, a small number of patients were still being exposed to a high radiation dose where combinations of skull and facial views were taken. Guidelines need to be subjected to regular audit.

Adolescent↗
PubMed2000

Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations.

There is wide variation in the management of patients with mechanical prosthetic valves who are taking anticoagulants and who require non-cardiac surgery. In this paper, we outline a pragmatic, practical approach to the adjustment of anticoagulation in relation to both the degrees of surgical trauma during oral and maxillofacial surgery and the risk of thromboembolism associated with the prosthetic valve. For minor surgery, no adjustment of anticoagulation is undertaken if the International Normalized Ratio is less than 4.0, if local haemostatic methods and tranexamic acid mouthwashes are used. For major surgery, warfarin is stopped preoperatively and low-molecular-weight heparin is used. For emergency surgery, partial reversal of anticoagulation with low-dose parenteral vitamin K is obtained.

Administration, Oral↗
PubMed2000

Effects of inspiratory flow on diaphragmatic motor output in normal subjects.

Increasing inspiratory flow (V) has been shown to shorten neural inspiratory time (TI(n)) in normal subjects breathing on a mechanical ventilator, but the effect of V on respiratory motor output before inspiratory termination has not previously been studied in humans. While breathing spontaneously on a mechanical ventilator, eight normal subjects were intermittently exposed to 200-ms-duration positive pressure pulses of different amplitudes at the onset of inspiration. Based on the increase in V above control breaths (DeltaV), trials were grouped into small, medium, and large groups (mean DeltaV: 0.51, 1.11, and 1.65 l/s, respectively). We measured TI(n), transdiaphragmatic pressure (Pdi), and electrical activity (electromyogram) of the diaphragm (EMGdi). Transient increases in V caused shortening of TI(n) from 1.34 to 1.10 (not significant), 1.55 to 1.11 (P < 0.005), and 1.58 to 1.17 s (P < 0. 005) in the small, medium, and large DeltaV groups, respectively. EMGdi measured at end TI(n) of the pulse breaths was 131 (P < 0.05), 142, and 155% (P < 0.05) of the EMGdi of the control breaths at an identical time point in the small, medium, and large trials, respectively. The latency of the excitation was 126 +/- 42 (SD) ms, consistent with a reflex effect. Increasing V had two countervailing effects on Pdi: 1) a depressant mechanical effect due primarily to the force-length (11.2 cmH(2)O/l) relation of the diaphragm, and 2) an increase in diaphragm activation. For the eight subjects, mean peak Pdi did not change significantly, but there was significant intersubject variability, reflecting variability in the strength of the excitation reflex. We conclude that increasing inspiratory V causes a graded facilitation of EMGdi, which serves to counteract the negative effect of the force-length relation on Pdi.

Adult↗
PubMed2000

Paclitaxel-associated hypersensitivity reactions: experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center.

PURPOSE: : This study expands the existing limited data as to whether patients developing clinically significant paclitaxel-induced hypersensitivity reactions can continue to be treated with this important antineoplastic agent and how such retreatment might be undertaken. PATIENTS AND METHODS: More than 450 patients received paclitaxel, either as a single agent or in a combination regimen, for a female pelvic malignancy in the Gynecologic Oncology Program of the Cleveland Clinic Cancer Center from January 1995 through December 1998. RESULTS: Of the more than 450 patients, 44 (approximately 9%) developed at least one episode of a clinically relevant hypersensitivity reaction to the cytotoxic drug. All 43 individuals (plus an additional four patients referred to our center after having previously experienced a severe paclitaxel-associated hypersensitivity reaction at another institution) who were retreated with paclitaxel were ultimately able to receive the agent. Five patients required treatment with a standardized desensitization regimen, developed by our group, to successfully receive paclitaxel. DISCUSSION: On the basis of this large single-institution study of paclitaxel-associated hypersensitivity reactions, we conclude that with appropriate precautions essentially all individuals experiencing these reactions can be safely treated with this agent.

Adult↗
PubMed2000

Phase I trial of paclitaxel plus megestrol acetate in patients with paclitaxel-refractory ovarian cancer.

Increased expression of P-glycoprotein has been proposed as one important mechanism for inherent or acquired drug resistance of malignant disease to cytotoxic chemotherapy. In experimental systems, hormonal agents, including megestrol acetate (MA), have been shown to be capable of reversing P-glycoprotein-mediated multidrug resistance to natural products, including paclitaxel. Because paclitaxel is one of the most active cytotoxic agents in ovarian cancer (OC), we sought to determine whether retreating patients with well-defined paclitaxel-resistant OC with a combination of paclitaxel and MA would result in clinically relevant reversal of that resistant state. In this Phase I trial, 44 patients with OC or primary peritoneal carcinoma received paclitaxel (135-175 mg/m2 over 3 h) plus an oral loading dose (800-9600 mg over 24 h) and subsequent maintenance dose (800-3200 mg/day x 3 days) of micronized MA. Both the loading dose and maintenance therapy were delivered in four equal daily doses. Therapy was repeated every 21 days, assuming recovery from the toxicity of the prior course. There were no intrapatient dose escalations. The major toxicity of the regimen was peripheral neuropathy (32% of patients; 11% grade 2-3), although four individuals developed major venous blood clots and one suffered a stroke. Four patients exhibited biological evidence of antineoplastic effects, although only one patient experienced improvement in clinically relevant symptoms. Although pharmacokinetic studies were not performed as a component of this study, prior evaluation of MA pharmacokinetics and in vitro data examining the concentrations of the agent required to reverse P-glycoprotein-mediated paclitaxel resistance suggest that the majority of our patient population achieved levels of MA theoretically capable of producing this desired effect. We conclude that the level of activity and toxicity pattern observed in this trial, associated with the combination of paclitaxel and MA, does not provide strong support for further exploration of the regimen as a treatment strategy to overcome paclitaxel resistance in OC.

Adult↗
PubMed1999

Use of low-dose oral prednisone to prevent paclitaxel-induced arthralgias and myalgias.

OBJECTIVES: The aim of this study was to examine the clinical utility of low-dose oral prednisone in preventing severe paclitaxel-associated arthralgias and myalgias. METHODS: Patients treated with paclitaxel in the gynecologic oncology program of the Cleveland Clinic Foundation who developed arthralgias/myalgias which were uncontrolled through the use of nonsteroidal anti-inflammatory medications received low-dose oral prednisone (10 mg B.I.D. starting 24 h after the completion of chemotherapy and continuing for a total of 5 days) with their next paclitaxel course. RESULTS: Of 46 patients meeting the criteria for treatment with the oral prednisone regimen (i.e., subjective feeling of unacceptable discomfort despite the use of nonsteroidal anti-inflammatory agents), 39 (85%) experienced substantial relief of symptoms. All but one of the responding patients requested continuation of the oral prednisone regimen with subsequent paclitaxel treatment cycles. There were no significant toxicities noted in any patient receiving prednisone. CONCLUSION: This low-dose oral prednisone regimen results in substantial improvement in the majority of patients experiencing significant paclitaxel-associated arthralgias/myalgias.

Administration, Oral↗
PubMed1999

Persistent chemosensitivity to platinum and/or paclitaxel in metastatic endometrial cancer.

It has long been recognized that individuals with ovarian cancer who initially respond to a platinum-containing chemotherapeutic regimen may exhibt a second response to platinum (cisplatin or carboplatin) at the time of recurrence. In this report, we describe three individuals with metastatic endometrial cancer who demonstrated secondary responses to platinum/paclitaxel-based regimens. Endometrial cancer should be added to the list of malignancies for which platinum and/or paclitaxel are considered as second-line treatment options in patients previously responding to the agents.

Adenocarcinoma↗
PubMed1999

An effective and more convenient drug regimen for prophylaxis against paclitaxel-associated hypersensitivity reactions.

"Standard" prophylaxis for paclitaxel-associated hypersensitivity reactions has included the systemic administration of H1 and H2 histamine antagonists, along with oral dexamethasone taken both the night prior to, and the morning of, each paclitaxel treatment. To improve patient convenience and compliance with steroid delivery, the Gynecologic Cancer Program of the Cleveland Clinic Foundation has treated patients with an all-intravenous prophylaxis regimen (diphenhydramine 50 mg, famotidine 20 mg, dexamethasone 20 mg) given 30 min prior to paclitaxel (without any earlier oral steroid dosing). To date, we have treated more than 200 patients who received all courses of paclitaxel with this simplified prophylactic regimen, of whom approximately 9% developed hypersensitivity reactions (major or minor). This incidence is comparable to our previously reported experience with hypersensitivity reactions in a similar number of patients receiving the standard prophylaxis (including oral dexamethasone) with their initial course of paclitaxel, and subsequent cycles employing this all-intravenous program. We conclude that this "modified" regimen for paclitaxel-associated hypersensitivity reactions (with all drugs administered approximately 30 min prior to the delivery of paclitaxel) is as effective as, and more convenient than, the standard regimen, and avoids delaying chemotherapy as a result of a patient failing to remember to take one or both oral steroid doses.

Anti-Inflammatory Agents↗
PubMed1999

Serum CA-125 as a marker of disease activity in uterine papillary serous carcinoma.

Papillary serous carcinoma of the endometrium exhibits many clinical features of ovarian cancer, including a high metastatic potential and response to platinum-based chemotherapy. We investigated the clinical utility of the serum CA-125 antigen level, an established marker of response or progression in ovarian cancer, to serve as a indicator of these events in patients with this highly malignant subtype of endometrial cancer. Of 21 individuals with this cancer treated in our program from 11/91 to 6/97, 16 had baseline CA-125 determinations prior to the administration of chemotherapy, of whom 13 were elevated above the normal range. Of these 13 patients, 8 (57%) experienced either a major reduction or normalization of CA-125 levels following therapy, consistent with their clinical course at that point in time. Similarly, of 11 patients who ultimately relapsed, 8 (73%) were found to have a rise in the CA-125 antigen level which closely corresponded to, or proceeded, clinical relapse. A single patient was demonstrated to have disease progression with a declining level of CA-125. We conclude the serum CA-125 antigen level is a useful indicator of disease response or progression in individuals with papillary serous carcinoma of the endometrium.

Aged↗
PubMed1999

Use of subcutaneous terbutaline to reverse peripheral ischemia.

Four cases are presented, one involving extravasation of a dopamine and dobutamine solution in the arm and three involving accidental digital injection of epinephrine into the thumb. In three cases, local infiltration of terbutaline resulted in dramatic reversal of vasospasm and ischemia. In the remaining case the use of terbutaline resulted in minor clinical improvement. These are the first reported cases involving the successful treatment of peripheral ischemia with subcutaneous terbutaline. This experience suggests that terbutaline may be an effective alternative for treatment of peripheral ischemia when phentolamine is not available.

Adolescent↗
PubMed1999

Anchoring the detached temporalis muscle in craniofacial surgery.

The temporalis muscle is often detached to enable craniofacial tumour and trauma access surgery. Failure to carefully handle and reattach the muscle often leads to a cosmetic and functional deformity. The authors discuss the principles of elevation of the whole temporal muscle within its surrounding fascia to reduce atrophy. The temporalis muscle is then reattached to its point of origin, using suspensory absorbable sutures attached to 3 mm titanium microscrews placed inferior to the limits of the muscle, to make them non-palpable. The aim is to reduce the postoperative temporal hollowing often seen when these principles are not observed. A series of cases using this technique are reported.

Adolescent↗
PubMed1999

Using cross-cultural input to adapt the Functional Assessment of Chronic Illness Therapy (FACIT) scales.

Cross-cultural quality of life measurement and psychosocial assessment in oncology have become reality with the translation and international validation of quality of life questionnaires. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, under development since 1987, produced its 4th version in November 1997. The FACIT system includes the Functional Assessment of Cancer Therapy (FACT), the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) and the Functional Assessment of Multiple Sclerosis (FAMS). These questionnaires were developed in North America and, to date, many have been translated into almost 30 languages. One of the strengths of this ongoing translation project is its use of input from patients, linguists, psychologists and physicians internationally to assure that the wording of Version 4 is more cross-culturally relevant and more sensitive to measuring the psychosocial impact of illness in cultures outside the United States. Statistical analysis, aggregation of patient comments, and comments from linguists and users of the translated versions are used as needed to revise item wording to ensure clarity and consistency across languages. A 'decentering' approach is also used to adapt the source (English language) document in response to problems encountered during its translation.

Chronic Disease↗
PubMed1999

Medullary metastasis causing impairment of respiratory pressure output with intact respiratory rhythm.

We present an unusual case of weaning failure. A 67-yr-old man presented with confusion, hyponatremia, and hypercapnic respiratory failure that necessitated mechanical ventilation. CXR revealed a right hilar mass (non-small-cell carcinoma on biopsy). Level of consciousness improved with treatment of his hyponatremia. However, attempts at weaning were complicated by hypercapnia with no overt distress. Resistance and elastance were only slightly abnormal, excluding mechanics as a cause of respiratory failure. Maximal inspiratory pressure (MIP) and vital capacity (VC) were reduced at -15 cm H2O and 0.97 L, respectively. Limb muscle strength was well preserved, suggesting isolated respiratory muscle weakness. During a weaning trial respiratory rate increased from 7 to 40 breaths/min as PCO2 increased from 56 to 89 mm Hg, confirming an intact respiratory pacemaker and good response to CO2. However, spontaneous Pdi was only 1 to 2 cm H2O (< 20% of Pdimax) despite profound hypercapnia. The fact that the patient did not utilize a greater fraction of his pressure-generating capacity suggested preferential impairment of the automatic respiratory centers. MRI showed a large central metastatic lesion in the rostral medulla with only a thin rim of uninvolved tissue. This case illustrates the utility of relating the magnitude of spontaneous efforts to maximal voluntary efforts as a means of localizing the site of involvement in cases of respiratory muscle weakness. It also demonstrates that a large medullary mass lesion may selectively impair brainstem modulation of respiratory pressure output while sparing other medullary functions, and in particular the pacemaking function of the respiratory centers.

Aged↗