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Biomedical subjects

K Webster

Publications and source records attributed to K Webster.

At least 55 records · Page 3Linked to original sources
PubMed1999

Response of ventilator-dependent patients to different levels of pressure support and proportional assist.

The ventilator's response to the patient's effort is quite different in proportional assist ventilation (PAV) and pressure support ventilation (PSV). We wished to determine whether this results in different ventilatory and breathing pattern responses to alterations in level of support and, if so, whether there are any gas exchange consequences. Fourteen patients were studied. Average elastance (E) was 22.8 (range, 14 -36) cm H2O/L and average resistance (R) was 15. 7 (range, 9-21) cm H2O/L/s. The highest PSV support (PSVmax) was that associated with a tidal volume (VT) of 10 ml/kg (20.4 +/- 3.2 cm H2O), and the highest level of PAV assist (PAVmax) was 78 +/- 7% of E and 76 +/- 7% of R. Level of assist was decreased in steps to the lowest tolerable level (PSVmin, PAVmin). Minute ventilation, VT, ventilator rate (RRvent), and arterial gas tensions were measured at each level. We also determined the patient's respiratory rate (RRpat) by adding the number of ineffective efforts (DeltaRR) to RRvent. There was no difference between PSVmin and PAVmin in any of the variables. At PSVmax, VT was significantly higher (0.90 +/- 0.30 versus 0.51 +/- 0.16 L) and RRvent was significantly lower (13.2 +/- 3.9 versus 27.6 +/- 10.5 min-1) than at PAVmax. The difference in RRvent was largely related to a progressive increase in ineffective efforts on PSV as level increased (DeltaRR 12.1 +/- 10.1 vs 1.4 +/- 2.1 with PAVmax); there was no significant difference in RRpat. The differences in breathing pattern had no consequence on arterial blood gas tensions. We conclude that substantial differences in breathing pattern may occur between PSV and PAV and that these are largely artifactual and related to different patient-ventilator interactions.

Aged↗
PubMed1999

Clinical features of hypersensitivity reactions to carboplatin.

PURPOSE: To characterize the clinical features of carboplatin-associated hypersensitivity reactions. PATIENTS: Patients with gynecologic malignancies treated at the Cleveland Clinic Foundation from June 1995 through July 1998 who experienced a carboplatin-associated hypersensitivity reaction were the subjects of this evaluation. RESULTS: Of the 205 patients treated with carboplatin during this time period, 24 (12%) developed a carboplatin hypersensitivity reaction. The median number of platinum (carboplatin plus cisplatin) courses for the first episode was eight (range, six to 21). Only three patients (13%) developed this toxicity during their initial chemotherapy regimen, with the remainder experiencing a reaction during their second (n = 15) or third (n = 6) carboplatin treatment program for recurrent disease. Thirteen patients (54%) developed at least moderately severe symptoms (diffuse erythroderma, tachycardia, chest tightness, wheezing, facial swelling, dyspnea, hypertension, or hypotension). In approximately one half of patients, the reaction developed after more than 50% of the carboplatin had been infused. Only one of three patients was successfully treated with the agent upon rechallenge. CONCLUSION: Carboplatin hypersensitivity reactions develop in patients who have been extensively pretreated with the agent. The clinical features are highly variable, but they are sufficiently different from those noted after the administration of paclitaxel that it should not be difficult to distinguish between reactions to the two agents. As carboplatin is increasingly used as initial and second-line chemotherapy of ovarian cancer and other malignancies, it can be anticipated that hypersensitivity reactions to the drug will become a more common and difficult clinical management issue.

Adult↗
PubMed1999

Nefazadone-induced acute dystonic reaction.

A 53-y-o patient presented approximately 2 h after taking her first dose of nefazadone. Chief complaint was lip smacking with hand and arm gesturing. The patient also took 25 mg meclizine which she had used before with no adverse effects. Diphenhydramine followed by benztropine led to resolution of symptoms within 1 h. Patient subsequently used meclizine with no untoward reactions. Nefazadone should be added to the list of agents that cause acute dystonic reactions.

Antidepressive Agents, Second-Generation↗
PubMed1999

The role of operator experience in fine needle aspiration cytology of head and neck masses.

Fine needle aspiration cytology (FNAC) was performed on 95 patients presenting with a mass in the head and neck region, where a subsequent surgical pathological diagnosis and adequate documentation were available. In this group, 70% of the samples were found to be of diagnostic yield. Of these, the number of true-positives was 27, and true-negatives 35. This gives a sensitivity and specificity of 90% and 97%, respectively. The accuracy was 100% when performed by a consultant and 91% when performed by junior staff. These sensitivity and specificity levels compare favourably with those reported in other studies using FNAC in head and neck lesions. Greater experience of the operator appears to improve the accuracy rate. FNAC is a useful diagnostic tool for head and neck tumours, as shown by the high specificity and sensitivity rates in this study.

Biopsy, Needle↗
PubMed1998

Phase 2 trial of moderately high dose single agent mitoxantrone in platinum and paclitaxel-refractory ovarian cancer.

In the human clonogenic assay, mitoxantrone possesses among the steepest dose-response curves of any cytotoxic agent against ovarian cancer. To test the potential clinical relevance of this observation, we conducted a phase 2 trial of moderately high dose single agent mitoxantrone (28 mg/m2 delivered every 3-4 weeks) along with granulocyte-macrophage colony stimulating factor (250 micrograms/m2/day beginning 24 h after mitoxantrone and continuing until neutrophil recovery) in 34 patients with clinically defined platinum and paclitaxel-refractory ovarian cancer. The major toxicity of treatment was severe neutropenia which was almost universal. However, there were no treatment-related infectious deaths. Significant cardiac toxicity was not observed. Five of 33 evaluable patients demonstrated objective evidence of a response to treatment (1 patient achieving a partial response of measurable tumor masses, 4 patients achieving a > or = 50% reduction in CA-125 antigen level), with a median duration of response of 3 months (range 2-5 months). We conclude that moderately high dose mitoxantrone has definite, although very limited, single agent activity in platinum and paclitaxel-refractory ovarian cancer. Unfortunately, as this regimen produces severe hematologic toxicity and response durations are short, it cannot be recommended for routine clinical use. The role of an even higher dose mitoxantrone schedule employed as a component of a high dose chemotherapy program with bone marrow or peripheral progenitor cell protection in the treatment of ovarian cancer remains to be defined.

Adult↗
PubMed1998

Phase 2 trial of single agent ifosfamide/mesna in patients with platinum/paclitaxel refractory ovarian cancer who have not previously been treated with an alkylating agent.

Ifosfamide has been shown to possess modest activity in patients with platinum/cyclophosphamide refractory ovarian cancer. Current standard initial chemotherapy for ovarian cancer does not include an alkylating agent (paclitaxel substituting for cyclophosphamide). To evaluate the activity of ifosfamide in patients with refractory ovarian cancer who had not previously received an alkylating agent, 21 patients with platinum/paclitaxel refractory disease were treated with the drug as a single agent (1.8 g/m2/day x 3 days, with treatment repeated every 28 days). Treatment was reasonably well tolerated in most patients, although 1 individual was removed from study secondary to neurotoxicity. One patient exhibited an objective response of measurable disease, while a second individual had a major decrease in CA-125 levels (no measurable disease present) following therapy. An additional patient experienced disappearance of severe pelvic pain following treatment but failed to meet the criteria for a partial response. We conclude that ifosfamide has modest activity in platinum/paclitaxel refractory ovarian cancer. However, the level of effectiveness does not appear to be increased in individuals who are alkylating-agent naive, compared to previously reported experience in patients with prior exposure to this class of cytotoxic drugs (10-15% response rate).

Adult↗
PubMed1998

Low-dose oral granisetron (1 mg) plus intravenous dexamethasone: efficacy in gynecologic cancer patients receiving carboplatin-based chemotherapy.

OBJECTIVE: The objective of this study was to determine the efficacy of a low-dose oral granisetron plus intravenous dexamethasone prophylactic antiemetic regimen in patients receiving carboplatin-based chemotherapy. PATIENTS AND METHODS: Patients with gynecologic malignancies being treated with either single-agent carboplatin or a carboplatin-paclitaxel regimen received a single 1-mg oral dose of granisetron 30 min prior to chemotherapy plus intravenous dexamethasone (20 mg) as prophylaxis for emesis. Patients either had not previously been treated with chemotherapy or had not received any cytotoxic drugs for >/=4 months prior to study entry. Effectiveness was evaluated based on the degree of control of nausea and vomiting during the 24 h following treatment. RESULTS: Of the 32 patients participating in this phase 2 trial, only 2 (6%) experienced any degree of nausea or vomiting within the first 24 h of chemotherapy administration. Both of these individuals had carcinomatosis and were experiencing emesis prior to chemotherapy. One patient developed mild delayed nausea >24 h after treatment. No major or minor toxic effects of the antiemetic regimen observed. CONCLUSION: A 1-mg dose of oral granisetron plus intravenous dexamethasone (20 mg) is a safe, effective, and relatively inexpensive prophylactic antiemetic regimen for patients receiving single-agent carboplatin or combination carboplatin-paclitaxel chemotherapy.

Adult↗
PubMed1998

Evidence that a "treatment-free interval of less than 6 months" does not equate with clinically defined platinum resistance in ovarian cancer or primary peritoneal carcinoma.

The standard definition of platinum-resistant ovarian cancer or primary peritoneal carcinoma commonly includes patients whose disease initially responded to a platinum-based combination regimen, but recurred less than 6 months after the completion of primary therapy. Recent experience with several patients with these malignancies treated in the Gynecologic Cancer Program of the Cleveland Clinic Foundation, whose disease recurred within this period but who subsequently responded to platinum therapy, calls into question the validity and clinical relevance of this commonly employed definition, both for the conduct of phase 2 trials of new agents in ovarian cancer and primary peritoneal carcinoma, and for the standard management of women in this clinical setting.

Aged↗
PubMed1998

Fetal oxygen saturation and fractional extraction at birth and the relationship to measures of acidosis.

OBJECTIVE: We sought to determine umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population and their predictive value for measures of acidosis. STUDY DESIGN: The computerized perinatal database of St. Joseph's Health Centre, London, Ontario, was used to obtain the umbilical cord gases, pH, mode of delivery, gestational age at delivery, and nuchal cord status for all live-born infants >500 gm between January 1991 and December 1995 (n = 22,134). Oxygen saturation values were calculated from the umbilical cord PO2 and pH data with a previously derived empirical equation, the accuracy of which was rechecked with 100 consecutive cord blood samples where oxygen saturation values were both calculated and measured with a hemoximeter (r = 0.99, p = 0.001). Fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data. RESULTS: There were 18,250 "validated" paired umbilical vein and artery blood gas and pH results available for analysis after patient case exclusions for missing, unreliable, or "unphysiologic" data. For all validated patient cases, mean umbilical vein oxygen saturation was 63% +/- 16% (SD), mean umbilical artery oxygen saturation was 24% +/- 15%, and mean fractional oxygen extraction was 0.62 +/- 0.20, with all three of these parameters significantly affected by mode of delivery, gestational age at delivery, and nuchal cord status. Umbilical vein and artery oxygen saturation and fractional oxygen extraction values showed significant relationships with umbilical artery base excess, albeit weak (r = 0.18 to 0.22), and pH (r = 0.46), which were best described using cubic regression models. Receiver-operator characteristic curve statistics for the prediction of acidosis at birth were also significant for all three of these parameters but lower when predicting metabolic versus mixed acidosis. However, all showed a poor positive predictive value for significant acidosis at birth, whether metabolic or mixed and regardless of the cutoff values used. CONCLUSION: Umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population indicate a decreased oxygen margin of safety for infants born postterm, by cesarean section after labor, and with a nuchal cord. However, these values have a limited relationship to measures of acidosis, which may have clinical implications for the usefulness of intrapartum pulse oximetry.

Acidosis↗
PubMed1998

The maxillofacial surgeon's guide to the Internet.

The use of computers has become an integral part of a clinician's work. A departmental or home computer linked to a modem allows the maxillofacial surgeon to access the wealth of clinical information and resources of the Internet. This article unravels some of the technology involved and acts as a guide for further exploration.

Computer Communication Networks↗
PubMed1998

Paclitaxel administration to gynecologic cancer patients with major cardiac risk factors.

PURPOSE: To examine the safety of administering paclitaxel to patients with preexisting significant cardiac risk factors. PATIENTS AND METHODS: The medical records of gynecologic cancer patients with major cardiac risk factors who had been treated with paclitaxel (single-agent or combination regimen with cisplatin or carboplatin) at The Cleveland Clinic Foundation from 1993 through February 1998 were examined to determine the acute toxicity of therapy. RESULTS: A total of 15 patients were found who met these criteria, of whom none were found to have suffered a worsening of cardiac function following treatment with paclitaxel. A single patient developed a severe paclitaxel-associated hypersensitivity reaction, but no cardiac sequela. CONCLUSION: This series suggests that paclitaxel can be safely administered as a single agent or in a combination regimen with a platinum agent to some patients with significant cardiac risk factors, such as those associated with ischemic heart disease. However, since few patients had baseline severe conduction defects before paclitaxel treatment, the safety of this drug in this clinical setting remains to be determined.

Aged↗
PubMed1998

Ninety-six-hour infusional paclitaxel as salvage therapy of ovarian cancer patients previously failing treatment with 3-hour or 24-hour paclitaxel infusion regimens.

PURPOSE: To test the hypothesis that prolonged infusion of paclitaxel (96 hours) might overcome resistance to shorter infusion schedules (3 or 24 hours) in ovarian cancer. PATIENTS AND METHODS: A total of 30 patients with advanced ovarian cancer (24 patients), primary carcinoma of the peritoneum (four patients), or fallopian tube cancer (two patients) who previously had received paclitaxel administered on either a 3-hour or 24-hour schedule were treated with the agent delivered as a 96-hour infusion (30 to 35 mg/m2/d x 4 days) on an every 3-week program. RESULTS: Although the regimen generally was well tolerated, no objective responses were observed. CONCLUSION: In patients with ovarian cancer who have shown resistance to shorter paclitaxel infusion schedules, ninety-six hour infusional paclitaxel is an inactive treatment strategy. This makes it less likely that protracted infusion of paclitaxel will improve outcome when used as part of primary therapy of ovarian cancer. An ongoing randomized study will answer that question.

Adult↗
PubMed1998

Preparation, attitudes and behaviour in nonhospital cardiac emergencies: evaluating a community's readiness to act.

OBJECTIVE: To determine how people in a moderately sized Ontario city believe they will react if they witness someone colapsing. DESIGN: Telephone survey. SETTING: The cities of Kitchener and Waterloo, part of the Regional Municipality of Waterloo, Ontario, with a combined population of 378,000. PARTICIPANTS: Households were randomly contacted and a questionnaire was administered, provided the respondent was over 44 years of age and agreed to be interviewed. Of 2479 households with eligible respondents, 811 (33%) completed the questionnaire. OUTCOMES: Age, sex, educational level, cardiac risk factors and cardiopulmonary resuscitation (CPR) training of respondents were determined, as well as actions they would take if cardiac arrest occurred in a family member at home or in stranger in the street, and associated emotions and barriers to implementing actions. RESULTS: Among the first three actions that respondents who were not prompted with possible responses said they would take, 311 (72%) witnessing a collapse at home, compared with 166 (44%) witnessing a collapse on the street, would call 911, the police or an ambulance. Other 'first three actions' in home collapse were checking for breathing (120 [28%]), checking for pulse (91 [21%]) and administering CPR (34 [8%]); these actions were less commonly selected in response to a strangers collapse and when respondents were not prompted. Respondents felt they would be more likely to perform CPR on a friend than on a stranger (OR 1.38, 95% CI 1.10 to 1.58). When asked how likely they would be to perform specific acts when witnessing a collapse, 254 (69%) of respondents thought they would call their family doctor and 179 (48%) thought they were likely to begin chest compressions. Barriers to performing CPR centred around legalities and disease transmission. CONCLUSION: Older people do not know how to act effectively in a cardiac emergency. Traditional CPR and public awareness programs have been ineffective in reaching this population; alternative means are required to help the public respond more effectively to cardiac emergencies.

Accidents↗
PubMed1998

Quality of life in patients with low-grade non-Hodgkin's lymphoma.

Low-grade non-Hodgkin's lymphoma (NHL) is an indolent form of the disease with a generally slow course of progression. Although still usually incurable, low-grade disease has shown responsiveness to some of the newer chemotherapeutic and nonchemotherapeutic treatment options. However, since cure remains elusive, and since many patients with lowgrade NHL may have few or even no symptoms initially, the decision about whether or not to initiate treatment logically must include quality-of-life (QOL) issues. This paper summarizes clinical and diagnostic characteristics of low-grade NHL that have some bearing on QOL considerations. Adverse effects of the more common treatment approaches are discussed according to their QOL implications, illustrating the relevance of QOL to the clinical management of low-grade disease. Finally, data from an ongoing study using the Functional Assessment of Cancer Therapy (FACT) measurement system are presented. These data offer a basis for comparing the QOL of patients with NHL to that of individuals with other solid tumors, and also illustrate the effects of chemotherapy on QOL.

Humans↗
PubMed1997

DNA binding and bending by the human papillomavirus type 16 E2 protein. Recognition of an extended binding site.

The human papillomavirus (HPV) 16 E2 protein (hE2) binds to four sites present upstream of the P97 promoter and regulates transcription of the viral E6 and E7 oncogenes. We have determined the relative binding constants for the interaction of the full-length hE2 protein with these sites. Our results show that hE2 binds tightly to site 4, less tightly to sites 1 and 2, and weakly to site 3. Similar results have previously been obtained using a C-terminal fragment of the hE2 protein suggesting that the C-terminal domain is the sole determinant of DNA binding affinity and specificity. Using circular permutation assays we show that binding of the hE2 protein induces the formation of a significant DNA bend and that the hE2-induced DNA bend angle is the same at both tight and weak hE2-binding sites. An alignment of the four hE2-binding sites from the HPV 16 genome suggests that this protein recognizes an extended binding site when compared with the bovine papillomavirus E2 protein. Here we show that the hE2 protein binds tightly to sites containing an A:T or a G:C base pair at position 7 of its binding site but weakly to sites containing either C:G or T:A at this position. Using site-directed mutagenesis we demonstrate that an arginine at position 304 of the hE2 protein is responsible for the recognition of specific base pairs at this position.

Binding Sites↗
PubMed1997

Continued chemosensitivity to cisplatin/carboplatin in ovarian carcinoma despite treatment with multiple prior platinum-based regimens.

While it is well recognized that individuals with ovarian cancer who have previously responded to platinum-based therapy can achieve a second response to cisplatin or carboplatin at the time of relapse, limited data exist in the oncologic literature regarding the number of times this process can be repeated. We briefly report here three patients with ovarian cancer currently being cared for in the Gynecologic Oncology program of the Cleveland Clinic Foundation who have achieved four (1 patient) or five (2 patients) separate clinical responses to cisplatin or carboplatin-based chemotherapy and have survived >4 years since the date of first relapse. This experience emphasizes the point that platinum resistance cannot be defined based on total treatment courses or the number of prior platinum-based regimens delivered, but only by objective evidence of failure of the drugs in an individual patient.

Aged↗