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Biomedical subjects

K Webster

Publications and source records attributed to K Webster.

At least 19 recordsLinked to original sources
PubMed2006

Measuring the impact of intimate partner violence on the health of women in Victoria, Australia.

OBJECTIVE: Using burden of disease methodology, estimate the health risks of intimate partner violence (IPV) among women in Victoria, Australia. METHODS: We calculated population attributable fractions (from survey data on the prevalence of IPV and the relative risks of associated health problems in Australia) and determined health outcomes by applying them to disability-adjusted life year estimates for the relevant disease and injury categories for Victoria, Australia for 2001. FINDINGS: For women of all ages IPV accounted for 2.9% (95% uncertainty interval 2.4-3.4%) of the total disease and injury burden. Among women 18-44 years of age, IPV was associated with 7.9% (95% uncertainty interval 6.4-9.5%) of the overall disease burden and was a larger risk to health than risk factors traditionally included in burden of disease studies, such as raised blood pressure, tobacco use and increased body weight. Poor mental health contributed 73% and substance abuse 22% to the disease burden attributed to IPV. CONCLUSION: Our findings suggest that IPV constitutes a significant risk to women's health. Mental health policy-makers and health workers treating common mental health problems need to be aware that IPV is an important risk factor. Future research should concentrate on evaluating effective interventions to prevent women being exposed to violence, and identifying the most appropriate mental health care for victims to reduce short- and long-term disability.

Adolescent↗
PubMed2006

Practical experiences of moving molecular diagnostics into routine use at the Veterinary Laboratories Agency.

The practical bench application of molecular tests (here defined as nucleic acid-based tests) in a routine testing situation is not without its challenges. This paper outlines the approaches we take at the Veterinary Laboratories Agency (VLA) and highlights some of the practical issues which we have found to be important for the successful introduction and use of molecular tests in a routine testing environment. The potential advantages of molecular tests, and factors which dictate which tests are adopted for routine testing, are discussed before giving some examples of molecular tests in routine use at the VLA. The instrumentation, reagents and assays we use are outlined, followed by sections of how we approach validation and how we manage and resource the transfer of molecular tests into routine use.

Laboratories↗
PubMed2005

Nicorandil induced oral ulceration.

Oral ulceration has many different causes. The association between Nicorandil and oral ulceration is not a new phenomenon. There have been several previous case reports regarding a possible association although none in publications for general dental practice. In this report we have a case series of seven patients and we compared our findings with those in the current literature.

Aged↗
PubMed2002

Links between anaesthetic modality and nerve damage during lower third molar surgery.

OBJECTIVE: To investigate the relationships between eruption status, gender, social class, grade of operator, anaesthetic modality and nerve damage during third molar surgery. DESIGN: Two centre prospective longitudinal study. SETTING: The department of oral and maxillofacial surgery, University Hospital Birmingham NHS Trust and oral surgery outpatient clinics at Birmingham Dental Hospital. SUBJECTS: A total of 391 patients had surgical removal of lower third molars. Sensory disturbance was recorded at one week post operatively. Patients with altered sensation were followed up at one month, three months and six months following surgery. RESULTS: 614 lower third molars in 391 patients were removed. Forty-six procedures (7.5%) were associated with altered sensation at one week with three procedures (0.49%) showing persistent symptoms at six months. Of these 46 nerve injuries, 26 (4.23%) involved the lingual nerve and 20 (3.25%) the inferior dental nerve (IDN). All three persistent sensations were IDN related. A logistic regression model found that the use ofa lingual retractor chi2 = 11.559, p = 0.003 was more significant than eruption status chi2 = 12.935, p = 0.007. There was no significant relationship between anaesthetic modality, age, social class, sex and seniority of operator. CONCLUSIONS: There was no link between the choices of local or general anaesthesia and nerve damage during lower third molar removal when difficulty of surgery was taken into account.

Adolescent↗
PubMed2001

A method for measuring passive elastance during proportional assist ventilation.

There are currently no reliable, noninvasive ways to monitor respiratory elastance (E) during assisted ventilation. We describe a method that is suited for proportional assist ventilation (PAV). In this mode, the end of the ventilator's inflation phase occurs during the declining phase of inspiratory effort (Pmus). If the opening of the exhalation valve is delayed, airway pressure (Paw) should initially rise as Pmus continues its decline. When Pmus declines to zero, a Paw plateau should appear. Paw at this point should reflect passive recoil at the prevailing volume. A cohort of 74 ventilator-dependent patients, ventilated in the PAV mode, were studied. Brief end-inspiratory occlusions were applied at random intervals. The magnitude of early change in Paw during the occlusion was inversely related to level of assist (r = 0.7, p < 0.00001). At high assist (> 75%), Paw was nearly flat or declined slightly, indicating minimal residual Pmus at the onset of occlusion. At lower assist levels, Paw increased exponentially in most patients with an average time constant of 0.21 +/- 0.06 s. Extraneous events that may corrupt the measurement (e.g., behavioral responses) were extremely rare (< 0.5%) in the first 0.25 s. From these findings, we concluded that Paw measured 0.25 s from occlusion onset (P0.25) includes little inspiratory Pmus and is free of extraneous events. E, estimated from P0.25 during PAV (EPAV), agreed well (r = 0.92) with passive E measured during controlled ventilation (ECMV); the average difference (EPAV - ECMV) was (+/- SD) -0.3 +/- 4.9 cm H2O x L(-1), corresponding to 0.9 +/- 16.4% of average E. We conclude that Paw measured at 0.25 s from the onset of end-inspiratory occlusion in the PAV mode provides a reliable estimate of passive elastic recoil.

Adult↗
PubMed2001

Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum.

PURPOSE: Standard chemotherapy for advanced ovarian cancer currently includes a platinum agent (usually carboplatin) and paclitaxel. Because docetaxel is an active agent in platinum-resistant ovarian cancer, it is relevant to evaluate both the toxicity and efficacy of the combination of carboplatin and docetaxel in this clinical setting. PATIENTS AND METHODS: The Gynecologic Oncology Program of the Cleveland Clinic Taussig Cancer Center conducted a phase II trial of carboplatin (area under the concentration-versus-time curve of 6) and docetaxel (60 mg/m(2)), delivered every 3 weeks for six courses, in patients with ovarian and fallopian tube cancers and primary carcinoma of the peritoneum who had either received no prior chemotherapy or had experienced a treatment-free interval of greater than 2 years before developing disease recurrence. RESULTS: Fifty patients (median age, 57 years; range, 44 to 81 years) entered the trial (47 had had no prior chemotherapy). Our toxicity findings included the following: grade 4 neutropenia (64% of patients); hypersensitivity reactions (34%, none requiring discontinuation of therapy); peripheral neuropathy (6%). We had objective responses for 32 of 42 (81%) assessable patients. CONCLUSION: The combination of carboplatin and docetaxel is highly active in ovarian cancer, with the major toxicity being bone marrow suppression. Hypersensitivity reactions are frequent but do not prevent continuation of treatment. With the dose and schedule employed in this trial, neurotoxicity is uncommon. Defining a role for this regimen in routine clinical practice will require the conduct of randomized controlled clinical trials.

Adult↗
PubMed2001

Reliability and validity of the functional assessment of cancer therapy-ovarian.

PURPOSE: To report the reliability and validity of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) in a consecutive series of outpatients with epithelial ovarian cancer. PATIENTS AND METHODS: Two hundred thirty-two ovarian cancer patients attending an outpatient gynecologic oncology clinic completed questionnaires at baseline. The patients' FACT-O scores were compared with their performance status, disease stage, treatment status, and other factors hypothesized to be related to quality of life. Patients received a second questionnaire either one week after baseline to assess the instrument's test-retest reliability and/or two months after baseline to evaluate its sensitivity to change in performance status. RESULTS: Internal consistency and test-retest reliability of the FACT-O were adequate. Overall, the scales correlated with other measures as expected; all correlations were in the hypothesized direction. Patients with advanced disease, poor performance status, and who were receiving active treatment had lower scores on physical, functional, and ovarian cancer-specific scales. The total FACT-O and emotional well-being scores were lower for patients with poor performance status and patients in active treatment. The FACT-O total and all subscale scores except emotional well-being were sensitive to decreases in performance status. CONCLUSION: Overall, the FACT-O provides a reliable and valid assessment of the quality of life of women with ovarian cancer, and is appropriate as a brief quality of life assessment in clinical trials and descriptive studies.

Activities of Daily Living↗
PubMed2001

Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids.

Lysophospholipids (lyso-PLs), including various glycerol-based and sphingosine-based lysophospholipids, play important roles in many biochemical, physiological, and pathological processes. The classical methods to analyze these lipids involve gas chromatography and/or high-performance liquid chromatography, which are time-consuming, cumbersome, and sometimes inaccurate due to the incomplete separation of closely related lipid species. We now describe the quantitative analysis of lyso-PLs in ascites samples from patients with ovarian cancer using electrospray ionization spectrometry. Three new classes of lyso-PL molecules are detected: alkyl-LPA, alkenyl-LPA, and methylated lysophosphatidylethanolamine. Importantly, the following lysophospholipid species are significantly increased in ascites from patients with ovarian cancer, compared to patients with nonmalignant diseases (e.g., liver failure): LPA (including acyl-, alkyl-, and alkenyl-LPA species), lysophosphatidylinositol, and sphingosylphosphorylcholine. Lysophosphorylcholine contents are also significantly different among ascitic fluids from the two groups of patients. However, the total phosphate content in ascites samples from patients with ovarian cancer is not significantly different compared to that from patients with nonmalignant disease.

Ascites↗
PubMed2001

Neurotoxicity associated with a regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) employed in the treatment of gynecologic malignancies.

While the combination chemotherapy regimen of carboplatin (AUC 5-6) and paclitaxel (175 mg/m2 over 3 h) is widely employed in the treatment of ovarian cancer, there are limited data available in the oncologic literature regarding the neurotoxic potential of the program. We retrospectively reviewed the clinical course of 87 patients treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center to address this important clinical issue. The overall incidence of peripheral neuropathy in this population was 25%, with 13% of women experiencing symptoms > or = grade 2 in severity. We conclude that while neurotoxicity is common following the use of this regimen, significant neurological dysfunction (> or = grade 2) is relatively infrequent.

Adult↗
PubMed2001

A method for noninvasive determination of inspiratory resistance during proportional assist ventilation.

Currently available noninvasive methods for measuring inspiratory resistance (RI) are difficult to implement or interpret during assisted mechanical ventilation on account of the confounding effect of respiratory efforts (Pmus). We propose a simple method consisting of brief reductions in airway pressure (Paw) in the early part of the inflation phase (pulse). Paw, flow (V), and volume (V) are measured at the beginning of the pulse (T (0)), at the trough of the pulse (TI) and at a point 0.1 s before T(0) (T(-1)). Equations of motion of the form [Pmus + Paw = V. K(1) + V (2). K(2) +V. E] are generated for the data at the three time points (E = elastance, K(1) and K(2) are Rohrer's constants). These three equations can be solved for K(1) and K(2) if it is arranged that the pulse has appropriate configuration and timing, and if it is assumed that DeltaPmus/Deltat is constant over the brief pulse period. The method was tested in 67 patients ventilated with proportional assist ventilation (PAV). The results were compared with those obtained using the interrupter technique during a period of controlled mechanical ventilation (CMV). RI, expressed at a standard flow of 1 L. s(-)(1), was slightly higher during PAV (16.4 +/- 4.9 versus 15.5 +/- 4.5 cm H(2)O. L(-1). s, p < 0.001). The average difference was 0.9 +/- 2.0 cm H(2)O. L(-1). s, corresponding to 5.4 +/- 12.6% of the average of RCMV and RPAV. The correlation coefficient was 0.92 (p = 8E-28) with a slope (1.01) and intercept (0.8) not significantly different from 1.0 and 0, respectively. We conclude that brief negative pulses applied early during the inflation phase can be used to provide reliable estimates of inspiratory resistance during PAV.

Airway Resistance↗
PubMed2000

The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway.

The human papillomavirus (HPV) E2 protein regulates viral gene expression and is also required for viral replication. HPV-transformed cells often contain chromosomally integrated copies of the HPV genome in which the viral E2 gene is disrupted. We have shown previously that re-expression of the HPV 16 E2 protein in HPV 16-transformed cells results in cell death via apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by overexpression of the HPV 16 E6 protein, but is increased by overexpression of wild-type p53. We show that mutations that block the DNA binding activity of E2 do not impair the ability of this protein to induce apoptosis. In contrast, removal of both N-terminal domains from the E2 dimer completely blocks E2-induced cell death. Heterodimers formed between wild-type E2 and N-terminally deleted E2 proteins also fail to induce cell death. Our data suggest that neither the DNA binding activity of E2 nor other HPV proteins are required for the induction of apoptosis by E2 and that E2-induced cell death occurs via a p53-dependent pathway.

Animals↗
PubMed2000

Declining CA-125 in an ovarian cancer patient with progression of measurable disease: a rational hypothesis for discordant results.

OBJECTIVES: While a declining CA-125 has been demonstrated to be a useful indicator of response to chemotherapy in ovarian cancer, occasional patients will demonstrate discordant results between the level of this antigen and changes in the size of measurable tumor masses. CASE: The patient was seen in the Gynecologic Oncology Program of the Cleveland Clinic Taussig Cancer Center. RESULTS: This patient exhibited a "major response" by CA-125 criteria, significant shrinkage of multiple peritoneal and perirectal implants, but clear progression of a pelvic side wall mass. The discordant results in this case are likely an example of a "mixed response" to the chemotherapy regimen, with the declining CA-125 corresponding to shrinkage of the responding tumor cell population. CONCLUSION: An evaluation of changes in both the serum CA-125 level and measurable masses may represent a more complete analysis of the status of disease in an individual with ovarian cancer.

Adult↗
PubMed2000

The antiemetic efficacy of oral ondansetron plus intravenous dexamethasone in patients with gynecologic malignancies receiving carboplatin-based chemotherapy.

PURPOSE: The purpose of this study was to develop a cost-effective prophylactic antiemetic regimen for the prevention of carboplatin-induced emesis. METHODS: Patients being treated in the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center with a carboplatin-based chemotherapy regimen received a prophylactic antiemetic program consisting of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) approximately 30 min prior to chemotherapy. Evaluation of the effectiveness of this antiemetic regimen was performed during a single treatment course. RESULTS: A total of 27 patients (median age, 62; range, 41-83) participated in this phase 2 trial. Three patients received single-agent carboplatin, and 24 were treated with either a carboplatin/paclitaxel or carboplatin/docetaxel regimen. The carboplatin AUC dosing level was 4, 5, or 6 in 6, 5, and 16 individuals, respectively. No patient developed vomiting; 2 (7%) individuals experienced nausea during the 24-h period following chemotherapy administration. CONCLUSION: The combination of a single dose of oral ondansetron (16 mg) plus intravenous dexamethasone (20 mg) is an effective prophylactic antiemetic regimen for patients receiving carboplatin-based chemotherapy.

Administration, Oral↗
PubMed2000

Phase 2 evaluation of topotecan administered on a 3-day schedule in the treatment of platinum- and paclitaxel-refractory ovarian cancer.

UNLABELLED: PURPOSE; The aim of this study was to investigate the toxicity and efficacy of a more convenient topotecan administration schedule (in contrast to the "standard" 1.5 mg/m(2)/day x 5 days q 21 days) in the management of platinum- and paclitaxel-refractory ovarian cancer. METHODS: Patients with clinically defined platinum- and paclitaxel-refractory ovarian cancer participating in this phase 2 trial conducted by the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center received topotecan at a dose of 1.5 mg/m(2)/day x 3 days on a 21-day schedule. Both dose escalations and reductions were permitted in the protocol design. RESULTS: A total of 29 patients (median age: 61; range: 43-80) were treated with this modified topotecan schedule. These individuals had received a median of two prior regimens (range: 1-4) (retreatment with a platinum agent or paclitaxel considered a single regimen). The median number of topotecan courses delivered was 3 (range: 1-7). Major toxicity included grade 4 neutropenia (24% of patients); neutropenic fever (10%); grade 3 thrombocytopenia (10%); and requirement for blood transfusion (14%). Dose escalation was possible, and dose reductions required, in 14 and 28% of patients, respectively. Two patients exhibited evidence of a clinically relevant response to treatment. CONCLUSION: This 3-day topotecan program is more convenient and less toxic than the standard 5-day regimen. The limited level of activity observed is not inconsistent with that previously reported for the 5-day topotecan infusion schedule in platinum/paclitaxel-refractory ovarian cancer. Further investigation will be required to document the clinical utility of a 3-day topotecan schedule in a less heavily pretreated and more chemosensitive patient population.

Adult↗
PubMed2000

Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum.

BACKGROUND: Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum-resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg/m(2) q 4 weeks) being severe erythrodysesthesia ("hand-foot syndrome") and stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well-defined patient population with platinum/paclitaxel-refractory disease. METHODS AND MATERIALS: Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum/paclitaxel-refractory disease (stable or progressive disease following treatment with these agents or previous objective response <3 months in duration) were treated with liposomal doxorubicin at a dose of 40 mg/m(2) q 4 weeks. RESULTS: A total of 49 patients (median age: 60; range 41-81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1-6). Six (12%) and 4 (8%) patients experienced grade 2 hand-foot syndrome and stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin administered on this protocol was 2 (range: 1-12). Four of 44 patients (9%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. CONCLUSION: This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well-defined platinum- and paclitaxel-refractory ovarian cancer.

Adult↗
PubMed2000

EMG biofeedback assisted KT-1000 evaluation of anterior tibial displacement.

Two studies were undertaken to evaluate the use of EMG biofeedback to encourage hamstring relaxation during KT-1000 measurement of anterior tibial displacement. In study 1, 60 ACL-deficient patients were studied in three groups using 15 lb and 20 lb in each group: in group 1 the patients were simply retested 15 min after the initial test sequence, in group 2 they were initially retested with EMG biofeedback and then again without, and in group 3 they were retested twice with EMG biofeedback. No significant difference in mean anterior tibial displacement was seen between the initial measurements and retest measurements when no EMG biofeedback was used. A significant increase in mean anterior tibial displacement was seen when the retesting was performed with EMG biofeedback. No further increase was seen with repeated retesting with EMG biofeedback. In study 2, 40 patients were evaluated 4-12 months following ACL reconstruction. KT-1000 measurements of anterior tibial displacement of both the operated and non-operated knees were made at 15 lb and 30 lb with and without the use of EMG biofeedback. EMG biofeedback was associated with a significant increase in unilateral measurement of anterior tibial displacement. When side-to-side differences were compared, there was a small but statistically significant increase in anterior tibial displacement with the use of EMG biofeedback. Although the use of EMG biofeedback to encourage hamstring relaxation does increase unilateral measurements of anterior tibial displacement, it does not appear to have a clinically significant effect on measurement of side-to-side difference. It may have a role in testing patients who have difficulty achieving hamstring relaxation or in aiding inexperienced examiners.

Adult↗