Search PubMed⌕ Search

Biomedical subjects

A Kennedy

Publications and source records attributed to A Kennedy.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ambulance economics.

BACKGROUND: Ambulance services produce a large quantity of data, which can yield valuable summary statistics. For strategic planning purposes, an economic framework is proposed, and the following four resource allocation questions are answered, using data from the Surrey Ambulance Service: (1) To satisfy government response time targets, how many additional ambulances will be required, ceteris paribus? (2) To minimize average response time (r*) with given resources, how should ambulances be rostered temporally? (3) Which innovations are worth undertaking? (4) How would an increase in demand affect r*? METHODS: The 'Ambulance Response Curve' --the relation between response time and the number of available but not-in-use ambulances--is used to estimate how much r* will be reduced by deploying an additional ambulance. Estimating the marginal cost of an ambulance allows us to estimate the opportunity cost of each second of response time, and to compare the cost of three 'innovations' with that of increasing resources. The time savings of adding an extra ambulance at each of the 168 h of the week are examined. RESULTS: In 1997-1998, r* was 8 min 52 s. An additional ambulance reduces r* by 8.9 s. Each reduction of 1 s in r* costs 28,000 pounds per year. Fourteen additional ambulances are required to meet response time targets if the 8.9 s reduction per ambulance is maintained. r* reduces by 4.6 s when ambulances are shifted from early mornings to Saturday evenings. Activation time reduces by 38 s when crews sit in their ambulances. A 1 min decrease in overall call time decreases r* by 1.1 s. Answering only 10 per cent of all calls reduces r* by 63 s. An increase of demand of 10 per cent increases r* by 7.8 s. CONCLUSIONS: Ambulance services will be better able to determine which innovations are worth undertaking. Policy makers will be better placed to determine funding levels to achieve response time targets.

Ambulances↗
PubMed2000

Postoperative endoscopic retrograde high dose-rate brachytherapy for cholangiocarcinoma.

Cholangiocarcinoma typically presents with disease unlikely to be completely resected, and prognosis remains poor. Improvements in imaging, endoscopy, and stenting have given rise to renewed interest in brachytherapy. Several recent retrospective series suggest a benefit to intraluminal brachytherapy, most commonly delivered by the transhepatic route. We describe a case in which brachytherapy was delivered via the nasobiliary route to address positive margins at the common bile duct stump. A custom catheter was manufactured to make the procedure feasible. Pertinent literature is reviewed, which supports the view that these malignancies benefit from high doses of radiation, if this can be achieved respecting normal tissue tolerance.

Aged↗
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

Tibiotalocalcaneal arthrodesis with intramedullary interlocking nail fixation.

The use of intramedullary rod fixation for tibiotalocalcaneal fusion is gaining popularity. Many methods of fixation have been employed in the past, but intramedullary fixation has been shown to achieve higher fusion rates, provide fixation along the weight-bearing axis, and control rotational deformities. The authors describe the history, indications, technical considerations, and postoperative care of patients treated with fixation using an intramedullary rod with interlocking screws.

Arthrodesis↗
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

Structural organization of the N-terminal domain of apolipoprotein A-I: studies of tryptophan mutants.

Site-directed mutagenesis and detailed fluorescence studies were used to study the structure and dynamics of recombinant human proapolipoprotein (proapo) A-I in the lipid free state and in reconstituted high-density lipoprotein (rHDL) particles. Five different mutants of proapoA-I, each containing a single tryptophan residue, were produced in bacteria corresponding to each of the naturally occurring Trp residues (position -3 in the pro-segment, 8, 50, 72, and 108) in the N-terminal half of the protein. Structural analyses indicated that the conservative Phe-Trp substitutions did not perturb the conformation of the mutants with respect to the wild-type protein. Steady-state fluorescence studies indicated that all of the Trp residues exist in nonpolar environments that are highly protected from solvent in both the lipid-free and lipid-bound forms. Time-resolved lifetime and anisotropy studies indicated that the shape of the monomeric form of proapoA-I is a prolate ellipsoid with an axial ratio of about 6:1. In addition, the region surrounding Trp 108 appears to be more mobile than the rest of the protein in the lipid-free state. However, in rHDL particles, no significant domain motion was detected for any of the Trp residues. The results presented in this work are consistent with a model for monomeric lipid-free proapoA-I in which the N-terminal half of the molecule is organized into a bundle of helices.

Amino Acid Substitution↗
PubMed1999

Use of subatmospheric pressure to prevent doxorubicin extravasation ulcers in a swine model.

UNLABELLED: Application of subatmospheric pressure to sites injected with doxorubicin prevented ulcer formation in treated sites (0 ulcers/16 sites) compared to control wounds (10 ulcers/16 sites) in a pig model. BACKGROUND AND OBJECTIVES: Extravasation of doxorubicin hydrochloride (Adriamycin) frequently causes chronic ulcers, which usually progress and expose underlying structures such as tendons and bone. The exact mechanism of action that causes cell death and the chronic ulcers is unknown. METHODS: Eight sites were injected intradermally with doxorubicin on each of 4 pigs. Four sites on each animal served as untreated controls. The remaining four sites were exposed to 125 mm Hg subatmospheric pressure applied 1 h after injection. The sites were observed on a three times per week schedule. Sites that did not develop ulcers were re-injected up to a total of four injections. The animals were observed for 5 weeks. RESULTS: Ten of sixteen control sites developed ulcers. No subatmospheric pressure treated sites developed ulcers. The incidence of ulcer formation was significantly less for treated wounds compared to control wounds at P < 0.001 by Fisher's exact test. CONCLUSIONS: This physical modality appears to successfully prevent ulcer formation after doxorubicin injection.

Animals↗
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

New HLA class II alleles in the Indonesian population.

This paper describes two new class II alleles of the major histocompatibility complex (MHC), DRB1*1431 and DRB3*0303, that have been found in the Indonesian population. In addition, the identification of DRB1*0819 is presented as a confirmatory report.

Alleles↗
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

The expression of inhibin/activin subunits in the human adrenal cortex and its tumours.

Inhibins and activins are dimeric proteins of the transforming growth factor-beta superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin alpha, betaA and betaB subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours. In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for beta subunits, suggesting that activins (beta beta dimers) can be expressed in all zones. Inhibin alpha was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins (alpha beta dimers) is restricted. Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both. Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin alpha in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin alpha in tumours associated with Cushing's syndrome again suggests a link with cortisol production.

Activins↗
PubMed1999

Is it better to leave or restore carious deciduous molar teeth? A preliminary study.

INTRODUCTION: The objective of this study was to compare the extraction and exfoliation experience of filled and unfilled carious deciduous molar teeth. METHOD: The study was carried out in 1997 in four general dental practices in south Cheshire, UK and involved a longitudinal retrospective review of case notes. A quota sample of 20 case notes of children from each practice was selected according to strict criteria. Subjects had to: Have had experience of approximal caries in one or more of the deciduous molar teeth. Have a date of birth between 1st January 1984 and 31st December 1985. Be a regular attender and in continuous contact with the practice. Data were collected on a common data abstraction form. Variables measured included: Base-line dmft. Site and number of filled teeth. Site and number of unfilled carious teeth. Number of courses of antibiotics. Site and number of pulp therapies. Site, number, method (local or general anaesthetic) of extractions. Reasons for extraction. All teeth not recorded as being extracted were assumed to have exfoliated. In addition, information was collected on the dentists' treatment philosophies. A series of group discussions revealed that the four dentists fitted into two groups according to treatment philosophies; two dentists shared a philosophy of minimal intervention, the other two shared the same views of treating more radically. RESULTS: There was no significant difference between the proportion of filled teeth and the proportion of carious unfilled teeth that were extracted (chi-square 0.05 P = 0.83). A logistic regression showed that for each course of antibiotics administered the odds of having an extraction was multiplied by 5.5 and children who were patients of the interventionist dentists were five times more likely to have an extraction than patients of non-interventionist dentists. CONCLUSION: Although the study was preliminary in nature no clear benefit could be found in filling deciduous molar teeth against leaving carious teeth unfilled, if avoidance of extraction was the desired outcome. The treatment philosophy of dentists was a major factor in determining extraction or exfoliation outcomes. This issue is complex with many interacting factors to be accounted for and will require multiple well-designed studies to provide an answer.

Anti-Bacterial Agents↗