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W Kennedy

Publications and source records attributed to W Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cost utility of chemotherapy and best supportive care in non-small cell lung cancer.

Polychemotherapy is the therapeutic option recommended for nonresectable, non-small cell lung cancer (NSCLC). However, the modest gains in survival, and the frequent and often serious adverse effects, associated with chemotherapy should also be considered when deciding on therapy. We therefore performed a cost-utility analysis of chemotherapy and best supportive care in NSCLC. Effectiveness and costs were analysed on 70 patients who were randomised to receive one of 3 treatments: VP (vindesine and cisplatin), CAP (cyclophosphamide, doxorubicin and cisplatin), or best supportive care. Subsequently, an assessment of the value of polychemotherapy and best supportive care was performed by oncology personnel using the time trade-off technique. Polychemotherapy was found to be more effective than best supportive care, but was also more costly and had a lower value score. Because of its cost utility and its higher value, best supportive care should not be discarded as an alternative for the treatment of NSCLC.

Antibiotics, Antineoplastic↗
PubMed1995

The economic effects of introducing vigabatrin, a new antiepileptic medication.

Epilepsy is a common disorder, the prevalence of which is estimated at between 0.1 and 1% of the population. Although there are a number of medications available for treating the disorder, 20 to 35% of affected individuals are resistant to standard treatments. Many of these patients could benefit from a new anti-epileptic, vigabatrin. Because the current indication for vigabatrin is as an adjunct in a specific subgroup of epileptic patients, which implies an increased cost of drug therapy, an ex ante economic appraisal of the expected consequences of its introduction in the treatment of epilepsy is valuable. This would provide decision makers with information to complement standard clinical data. Using administrative records of healthcare services utilisation by epileptic patients, we performed a simulation of the expected economic repercussions of vigabatrin use on direct costs related to disease management. The results show that whether or not the introduction of vigabatrin results in an increase or a reduction in costs to the healthcare system depends largely on 3 factors: (i) the administered dosage of vigabatrin; (ii) the effect that vigabatrin has on hospital admissions; and (iii) the proportion of epileptic patients who take the drug. Moreover, this study underlines the usefulness of administrative data in forecasting the economic impact of new health technologies.

Anticonvulsants↗
PubMed1995

Expression and in vitro regulation of integrins by normal human urothelial cells.

Integrins are thought to be essential adhesion receptors for the maintenance of tissue histioarchitecture. The purpose of this study was to determine integrin expression patterns in the human stratified transitional epithelium of the urinary tract (urothelium). In situ expression patterns were compared with in vitro expression, using a normal cell culture model system in which the effects of cell stratification can be studied independently of differentiation. By immunohistological criteria, the urothelia of bladder, ureter and renal pelvis expressed alpha 2 beta 1 and alpha 3 beta 1 integrins in all layers at intercellular junctions, and cytoplasmically in the lower strata. By contrast, alpha 6 beta 4 and occasionally alpha v beta 4 were expressed only by basal cells and localised to the basal lamina. These expression patterns were unaltered in specimens where an inflammatory cell infiltrate was present. In long-term cultures of normal urothelial cells maintained in a low-Ca++ serum-free medium, the monolayer cultures expressed alpha 2 beta 1, alpha 3 beta 1 and alpha 5 beta 1 integrins at intercellular junctions and in cytoplasmic inclusions, whereas alpha 6 beta 4 was distributed in a random pattern over the substratum. Increasing exogenous Ca++ concentrations induced cell stratification and desmosome formation, but not cytodifferentiation. Under these conditions, alpha 6 beta 4 became cell-, rather than substratum-associated, localising particularly to filopodia and lamellipodia. Quantitation of integrin expression by flow cytometry confirmed increased surface expression of alpha 6 beta 4 in high Ca++ media, and also of alpha 3 and alpha 5, but not alpha 2, subunits. These results suggest that alpha 2 beta 1 and alpha 3 beta 1 integrins, although differentially regulated, are mainly involved in homotypic cell-cell interactions and the maintenance of a stratified morphology, whereas alpha 6 beta 4 is the principal integrin involved in substratum adhesion.

Adolescent↗
PubMed1992

Phase I study of recombinant human interferon gamma in children with relapsed acute leukemia.

Fourteen children (ages 2-15 years) with acute leukemia in relapse were treated with daily recombinant interferon gamma for 14 days by subcutaneous injections at fixed dose levels of 0.1, 0.25, 0.5, or 0.75 mg/m2 (1.0, 2.5, 5.0, or 7.5 x 10(6) units/m2) without intrapatient escalation. Patients received a second 14-day course of therapy followed by thrice weekly administration unless there were signs of progressive disease or grade 3 or 4 toxicity. Side effects in the 13 evaluable patients included fever (n = 10), fatigue (9), decreased Karnofsky performance score (8), hypertriglyceridemia (8), myalgia (5), weight loss > 5% (4), elevated liver transaminases (4), and abdominal pain (3). There was only one grade 4 toxicity: one of the six patients at the 0.5 mg/m2 dose level developed reversible acute renal failure. One patient died of gastrointestinal hemorrhage due to disease-related refractory thrombocytopenia. One child had an oncolytic response and two others stable disease for 138 and 148 days. An appropriate dose level for phase II studies in children is 0.5 mg/m2 per day.

Adolescent↗
PubMed1991

Response to alpha-interferon in children with Philadelphia chromosome-positive chronic myelocytic leukemia.

The therapeutic efficacy and toxicity of alpha-interferon (alpha-IFN) (Roferon, Hoffmann-La Roche, Inc., Nutley, NJ) were determined in 15 children (age range, 6 to 20 years) with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML). All patients had received cytoreductive therapy with either hydroxyurea (n = 13) or busulfan (n = 1) or both (n = 1) for 6 weeks to 46 months (median, 7 months) before beginning alpha-IFN therapy at a dose of 5 x 10(6) U/m2/d intramuscularly. This dose was escalated to 10 x 10(6) U/m2/d if leukemia was inadequately controlled. Ten children had a hematologic response, with nine showing a reduction in the percentage of Ph+ marrow cells, including four who had no detectable Ph+ cells in marrow samples collected 48 to 204 weeks after the initiation of therapy. Two of 15 patients remain free of Ph+ cells. Therapy was discontinued before week 104 in ten patients because of the following: (1) early hematologic responses without a decrease in Ph+ cells (three patients); (2) early resistant disease (one patient); (3) blast crisis (one patient); (4) progressive disease (two patients); (5) seizure attributed to high-dose alpha-IFN (one patient); or (6) an inadequate trial of alpha-IFN caused by aseptic necrosis or poor compliance (two patients). The most common side effects were mild and have included fever, malaise, headache, myalgias, and pain at the injection site. Adverse events causing interruption of therapy were seizures, aseptic necrosis, and myelofibrosis. alpha-IFN stabilizes the chronic phase of Ph+ CML in some children, is adequately tolerated when administered at a dose of 2.5 to 5 x 10(6) U/m2/d intramuscularly, and results in a significant decrease in the proportion of Ph+ metaphases in some patients. alpha-IFN in combination with an effective cytoreductive agent or agents appears worthy of further clinical testing in this disease.

Adolescent↗
PubMed1991

Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men.

A hydroxynaphthoquinone compound (566C80) has been shown to be effective in the prevention and treatment of murine Pneumocystis carinii pneumonitis. In a phase I study, five cohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000 mg of the compound orally once daily for 12 days. A sixth cohort received 750 mg three times daily for 5 days, then twice daily for 16 days. Evaluation included clinical, hematologic, and biochemical studies and the pharmacokinetics of 566C80. The only drug-related adverse effect was a maculopapular rash in one patient that resolved without discontinuation of the drug. With the largest dosage tested (3000 mg) the following pharmacokinetic measures were achieved: maximum plasma concentration, 39 micrograms/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h.micrograms/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 l/h. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.

Adult↗
PubMed1991

In vivo and in vitro expression of Haemophilus influenzae type b lipooligosaccharide epitopes.

An indirect immunofluorescence system involving monoclonal antibodies (MAbs) directed against surface epitopes of Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS) was used to examine individual Hib cells in cerebrospinal fluid (CSF) from infants with Hib meningitis. In four of five CSF samples studied, 100% of the bacteria bound at least one LOS-directed MAb. When the bacteria from these CSF samples were grown in broth, most of these cells lost some or all of their ability to bind the MAb(s) that were bound by the same organisms present in human CSF. When in vitro-grown cells were used for intracisternal injection of rabbits, the populations of Hib cells observed in rabbit CSF after the development of meningitis generally resembled those of the respective broth-grown inocula in terms of their LOS antigenic characteristics. Hib cell populations recovered in infant rat CSF after intranasal challenge again had LOS antigenic characteristics similar to those of the in vitro-grown challenge inocula. These results indicate that a population of Hib cells growing in the infected human host may be quite different, with regard to its LOS antigenic characteristics, from the same Hib strain growing in vitro or in vivo in animal models.

Animals↗
PubMed1991

Decreased sweat-gland number and function in patients with alopecia areata.

In this study the number and function of sweat glands on the dorsum of the hand and foot were evaluated using a silastic imprint method. Twenty patients, 11 females and nine males with either alopecia areata, alopecia totalis, or alopecia universalis were included in the study. Patients showed a significant decrease in activated sweat-gland number and function compared to matched controls (P less than 0.001). There was no significant relationship between the degree of sweat-gland dysfunction and extent of hair loss, concurrent illnesses, or treatment. These findings suggest that eccrine sweat-gland function is compromised in patients with alopecia areata.

Adolescent↗
PubMed1989

A 10-year experience with 290 pancreas transplants at a single institution.

Since our report at the 1984 American Surgical Association meeting of 100 pancreas transplants from 1966 through 1983, another 190 have been performed. The current series, begun in 1978, now numbers 276 cases, and includes 133 nonuremic recipients of pancreas transplants alone (PTA), 46 simultaneous pancreas/kidney transplants (SPK), and 97 pancreas tranplants after a kidney transplant (PAK). Duct management techniques used were free intraperitoneal drainage in 44 cases, duct occlusion in 44, enteric drainage in 89, and bladder drainage in 128. The 1-year patient and graft survival rates in the entire cohort of 276 were 91% and 42%. One-year patient survival rates were 88% in the first 100, 91% in the second 100, and 92% in the last 76 cases; corresponding 1-year graft survival rates were 28%, 47%, and 56% (p less than 0.05). A prospective comparison of bladder drainage (n = 82) versus enteric drainage (n = 46) in PAK/PTA cases since November 1, 1984 favored bladder drainage (1-year graft survival rates of 52% vs. 41%) because of urinary amylase monitoring. The best results were in recipients of primary SPK bladder-drained transplants (n = 39), with a 1-year pancreas graft survival rate of 75%, kidney graft survival rate of 80%, and patient survival rate of 95%. Logistic regression analysis, with 1-year graft function as the independent variable, showed significant (p less than 0.05) predictors of success (odds ratio) to be technique: bladder drainage (5.8) versus enteric drainage (2.5) versus duct injection (1.0); category: SPK (6.0) versus PAK from same donor (3.2) versus PAK from different donor (1.2) versus PTA (1.0); and donor HLA DR mismatch: 0 (5.0) versus 1 (2.5) versus 2 (1.0) antigens. On April 1, 1989, 90 patients had functioning grafts (60 euglycemic and insulin-free for more than 1 year, 10 for 5 to 10 years); these, along with 24 others whose grafts functioned for 1 to 6 years before failing, are part of an expanding cohort in whom the influence of inducing a euglycemic state on pre-existing secondary complications of diabetes is being studied. Only preliminary data is available. In regard to neuropathy, at more than 1 year after transplant in patients with functioning grafts, conduction velocities in some nerves were increased over baseline. In regard to retinopathy, deterioration in grade occurred in approximately 30% of the recipients by 3 years, whether the graft functioned continuously or failed early, but thereafter retinopathy in the patients with functioning grafts remained stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗
PubMed1987

Effect of aryl 4-guanidinobenzoates on the acrosin activity of human spermatozoa.

Certain aryl 4-guanidinobenzoates (AGs; inhibitors of proteinases, including the sperm enzyme acrosin) have been shown to be more potent vaginal contraceptives in rabbits and less toxic than nonoxynol-9, the active ingredient of most marketed vaginal contraceptive formulations. To determine if these AGs can contact sperm and inhibit acrosin when mixed with the entire human ejaculate for a short period of time (roughly imitating clinical conditions), the inhibitors were added to semen at various concentrations for 2 min, after which the seminal plasma and unbound inhibitor were removed from the sperm by Ficoll centrifugation. Subsequently, the total arginine amidolytic activity of the spermatozoa was determined spectrophotometrically after a combined treatment that resulted in extraction, proacrosin activation, and reaction with substrate. Dose-response curves were prepared. All AGs studied were effective inhibitors of the amidolytic activity under these conditions, with ED50 values (the dose levels at which half of the acrosin associated with 10(6) sperm is inhibited) ranging from 10(-5) to 10(-7) M. To determine the effect on the proteolytic activity of individual spermatozoa, the experiment was repeated with 4'-acetamidophenyl 4-guanidinobenzoate (AGB), and the protease released from the sperm was measured by the gelatin-plate assay. The inhibition results were similar to those obtained by extraction of the spermatozoa and measurement of amidolytic activity. Thus, when mixed with the human ejaculate, AGs interact rapidly with spermatozoa to inhibit both their arginine amidolytic and proteolytic activity (probably due primarily or only to inhibition of acrosin) and remain bound even after removal of the seminal plasma. These data encourage further study of the compounds for contraceptive purposes.

Acrosin↗
PubMed1979

Isolated high serum triiodothyronine levels. Clinical relevance after sodium iodide I 131 therapy.

Ten of 25 thyrotoxic patients treated with sodium iodine I 131 had thyroid function test results that indicated a high triiodothyronine (T3) level, with normal thyroxine (T4) and thyroid-stimulating hormone (TSH) levels, within 15 months of treatment. This pattern was usually transitional and lasted a variable time, eventually leading to euthyroidism, hyperthyroidism, or hypothyroidism. It is concluded that an isolated elevation of T3 levels after radioactive iodine therapy can be associated with any clinical pattern of thyroid function and has no clear prognostic value. No specific treatment is needed for this abnormality.

Adult↗
PubMed1978

Prediction of late survival in patients with mitral valve disease from clinical, hemodynamic, and quantitative angiographic variables.

Late follow-up (average = 7.2 years) has been obtained in 249 patients with mitral valve disease who had quantitative angiographic assessment of left ventricular function at thetime of initial catheterization in the 1960s. Surgically treated patients with mitral valve disease had significantly improved survival as compared to medically treated patients with mitral disease. The subgroup with mixed mitral stenosis and regurgitation and the subgroup with moderate impairment of ejection fraction account for this improved survival in surgically treated patients, which occurred despite greater functional and hemodynamic impairment in the surgical cohorts. Using univariate life table survival analysis, ten variables were found to be predictive of survival in the medical cohort, and three in the surgical cohort. With multivariate Cox's regression analysis, end-diastolic volume and arteriovenous oxygen difference were significantly predictive of survival in the medical cohort; age was predictive of survival in the surgical cohort.

Hemodynamics↗
PubMed1977

Kidney transplantation for the uremic diabetic patient.

Although the diabetic patient is at high risk for transplantation and the progression of cardiovascular disease continues, results of our experience indicate that kidney transplantation can be performed with only slightly less favorable results than in the nondiabetic patients. We have found that the survival rate achieved by diabetics who receive a kidney graft is superior to that achieved by diabetic patients who receive dialysis. We also believe that some of the secondary complications of diabetes, which are aggravated by uremia, will be improved and that successful vocational rehabilitation is possible in the majority of diabetic patients.

Adult↗
PubMed1974

Fire in the OR.

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Accident Prevention↗