Practice guidelines given by specialty societies.
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Humans↗
Biomedical subjects
J Kavanagh
Publications and source records attributed to J Kavanagh.
Lesbians and cervical screening.
Confusion exists in clinical practice about whether lesbians should be offered routine cervical smears. We found cervical smear abnormalities in a sample of 624 lesbians, including those who had never been sexually active with men. These findings suggest that lesbians should be routinely offered cervical cytology as part of the national screening programme. Evidence of human papilloma virus (HPV) infection in the 'exclusively lesbian' group indicates that sexual transmission of HPV may occur between women. The belief by some lesbians that they have less need for cervical smears, coupled with poor uptake of cervical screening by a significant proportion, demonstrates a need for education of lesbians and health service providers.
Adult↗
Is there a positional fault at the inferior tibiofibular joint in patients with acute or chronic ankle sprains compared to normals?
The purpose of this study was to test the hypothesis that a positional fault occurs at the distal tibiofibular joint when the foot is inverted beyond its normal range (Mulligan 1995). Seventeen normal subjects, two subjects with a chronic tendency to 'go over' on one or both ankles and six patients with acutely sprained ankles were positioned in supine lying with the foot to be tested in the subtalar neutral position. An anteroposterior (AP) mobilization was then performed on the lateral malleolus of the right and left ankles of all those included in the study. The movement that occurred at the distal fibula as a result of this mobilization was recorded and plotted against the force required to produce it. The slopes of the graphs from the three groups of subjects were statistically analysed using the appropriate t tests. Results indicated that a significantly greater amount of movement per unit force occurred in one third of the patients with acutely sprained ankles (P = 0.01%, P = 0.09%). These results lend support to the hypothesis that a positional fault occurs at the inferior tibiofibular joint in ankle sprain patients. This could have exciting implications for the future direction of the treatment of these injuries.
Acute Disease↗
The anatomy of a healing garden.
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Health Facility Environment↗
Adolescents' perceptions of substance abuse prevention strategies.
As part of a 3-year evaluation of substance abuse prevention strategies (Harding, Safer, Kavanagh, Bania, Carty, Lisnov, & Wysockey, 1996), this study examined the perceptions of 719 sixth- through ninth-grade Chicago public school students. School-based programs were rated as significantly more effective on six prevention objectives than were television ads, testimonials by famous people, billboards, and print ads displayed on public transportation. Students perceived the two school-based programs, Project DARE (a national program conducted through local police departments) and Captain Clean (an intense live theater program coordinated with student participation), as being equally effective overall, although the interactive theater program was rated as significantly better at encouraging students to talk about their feelings concerning substance abuse issues and at relating to the students' ethnic/racial backgrounds. When students were categorized according to frequency of alcohol use, nonusers, infrequent users, and frequent users differed significantly in their ratings of the school-based programs.
Adolescent↗
Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer.
Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retroviral vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
New generation dopaminergic agents. 1. Discovery of a novel scaffold which embraces the D2 agonist pharmacophore. Structure-activity relationships of a series of 2-(aminomethyl)chromans.
A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high- and low-affinity agonist states (D2High and D2Low, respectively) of the dopamine (DA) D2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D2High receptor vs the 5HT1A and alpha 1 receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D2High receptor vs the alpha 1 and 5HT1A receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D2 agonist pharmacophoric criteria and was proposed as the D2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo- and hyperdopaminergic activity, without the side effects associated with complete D2 agonism or antagonism.
Animals↗
Dorzolamide hydrochloride and visual function in normal eyes.
PURPOSE: To determine by a pilot study whether standard treatment with the topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual function under normal breathing conditions, during carbon dioxide inhalation, or during hyperventilation, and to establish criteria for future larger-scale studies. METHODS: We enrolled 12 normal subjects into this randomized double-masked placebo-controlled crossover study. Each subject was treated with either dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout period, the alternative topical agent was used under identical testing conditions. On day 2 of each treatment phase, contrast sensitivities to sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4, mean deviation values from full-threshold 10-2 visual fields were obtained. Three sets of each visual function test were obtained before each treatment phase, and in sequence on each testing day, during normal breathing (baseline), inhalation of carbon dioxide-enriched air, and hyperventilation while intraocular pressure was monitored. RESULTS: Contrast sensitivity at 4 cpd decreased significantly (P < .01) during carbon dioxide supplementation with placebo but showed no significant change with dorzolamide. The decrease in contrast sensitivity accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry mean deviation values under each treatment condition and was statistically significant (P < .05) at baseline. CONCLUSIONS: Dorzolamide appears to enhance contrast sensitivity in normal subjects during physiologic hypercapnia and hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions, dorzolamide therapy increases perimetric light sensitivity.
Adult↗
Phase II trials of docetaxel (Taxotere) in advanced ovarian cancer--an updated overview.
Docetaxel (Taxotere) has been studied at a dose of 100 mg/m2 i.v. as a one hour infusion every 3 weeks, in four phase II trials in patients with extensively pretreated ovarian cancer. A total of 340 patients were treated, including 256 patients in two separate EORTC (European Organization for Research and Treatment of Cancer) trials and 84 patients in two trials in the U.S.A. All patients had received prior cisplatin or carboplatin therapy and the treatment-free interval was less than 4 months in 155 patients. The overall response rate using conventional UICC criteria was 30% among 315 evaluable cases (95% confidence interval: 24-36%). Among 155 patients whose disease was most refractory (i.e. treatment-free interval was less than 4 months), the overall response rate was 28% (95% confidence interval: 19-36%). Response duration ranged from 4 to 17 months. Grade IV neutropenia was a common finding and fluid retention was observed. The incidence of febrile neutropenia ranged from 8 to 44% of patients with two deaths (i.e. 0.6% of the total treated) related to neutropenic sepsis. Docetaxel and paclitaxel (Taxol) have comparable activities in ovarian cancer. Ongoing studies with docetaxel include its use in patients as part of first-line therapy, as well as in patients refractory to paclitaxel. To prevent the development of fluid retention, these now involve the routine use of steroid prophylaxis. It is expected that docetaxel will prove to be an important addition to the drugs available for the treatment of ovarian cancer.
Adult↗
A multicentre prospective study of prostatic volume in asymptomatic men in various continents.
Objective: To compare prostatic volumes in asymptomatic Asian men with similar controls in Europe. Patients and methods: Six centres (Beijing, Hong Kong, Jinan, Lisbon, Palermo and Stirling) independently selected asymptomatic men aged 55 y or more for assessment of prostatic volume using transrectal ultrasound (total=320 men) between 1992 and 1993. Results: Prostatic volumes in asymptomatic men were greater in Beijing than Hong Kong, Stirling and Palermo (P<0.05) and were smaller in Stirling than Beijing and Jinan (P<0.05). Conclusions: These results suggest that men from Stirling are less likely to have large prostates, but there is no evidence that men from any of the six cities are more likely to have small prostates. This small series may suggest that benign prostatic hyperplasia (BPH) is as common in China as in European cities. The differences may be due to some cities (Beijing, Jinan and Lisbon) having a greater proportion of high values, perhaps suggesting looser selection criteria. This may indicate an abandonment of traditional Asian foods with their presumptive beneficial effect in favour of a Western dietary style.
Journal Article↗
Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.
To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A case-controlled study of the sexual health needs of lesbians.
OBJECTIVES: To evaluate and compare the range of genital infections diagnosed in a group of lesbians attending an inner city genitourinary clinic with a control group of heterosexual women attending the same clinic. SETTING: The Ambrose King Centre, the Royal London Hospital, a genitourinary clinic within which the Audre Lorde Clinic, a specialist sexual health clinic for women identifying as lesbians, is operated. SUBJECTS: Two hundred and forty one women attending the specialist clinic between October 1993 and September 1994. Heterosexual controls matched for age and ethnicity were selected from the same time period. METHODS: A retrospective case note analysis was made of 241 lesbians and 241 matched heterosexual controls. Data were collected on age, ethnicity, symptoms, diagnoses and services used. RESULTS: An infection was diagnosed in 129 (65%) of the lesbians and 126 (62%) of the heterosexual women. Only 23 (10%) of the lesbians exclusively practised same gender sexual contact. Genital herpes (p = 0.05) and genital warts (p = 0.005) were more common in the heterosexual women. Gonorrhoea and chlamydia infection were infrequent diagnoses in both groups, occurring in four (2%) lesbians and 14 (7%) heterosexuals (p = 0.05). Bacterial vaginosis occurred in 65 (33%) of the lesbians and 27 (13%) of the heterosexuals (p < 0.0001). Cervical cytology abnormalities were uncommon but only found in the lesbians. CONCLUSIONS: Screening for genital infections in lesbians is appropriate. The high prevalence of bacterial vaginosis in this group is unexplained but suggests a possible sexual transmission. Lesbians should be included within the cervical cytology screening programme.
Adolescent↗
Using live theatre combined with role playing and discussion to examine what at-risk adolescents think about substance abuse, its consequences, and prevention.
Live theater is used as a means of stimulating thought and discussion among adolescents on topics related to the effects of substance abuse in their lives. A thirty-minute professional and contemporary live musical play, Captain Clean, was performed at three Chicago high schools (grades 9-12). In general, students in these schools had been judged to be at risk for drug problems by school administrators and by the Illinois Criminal Justice Information Authority. Students' responses to issues highlighted in the play were examined through ethnographic procedures used during role playing and discussion immediately following the performance. In addition, written comments were collected from the students two weeks after viewing. The amount of interaction and level of student response indicate that live theater is an effective means for stimulating both thought and discussion pertaining to the effects of drugs in the lives of adolescents. In addition, analysis of the students' responses reveals: (1) an unmet need for individual counseling; (2) a pervasive ignorance of the legal consequences of drug use; (3) the importance of family as a source of information and support; and (4) an expressed concern for their own futures as well as those of their peers.
Adolescent↗
Docetaxel in advanced ovarian cancer: preliminary results from three phase II trials. EORTC Early Clinical Trials Group and Clinical Screening Group, and the MD Anderson Cancer Center.
Docetaxel has been evaluated in 293 patients with advanced ovarian cancer in three phase II trials. All patients had previously received cisplatin and/or carboplatin as first-line treatment. In all three studies, treatment comprised docetaxel 100 mg/m2 as a 1 h intravenous infusion every 3 weeks, without premedication for hypersensitivity reactions or emesis. To date, 200 patients are evaluable for response. Of these, 63 patients achieved complete or partial response, giving an overall response rate of 31.5% (95% confidence interval 24-39%) for all evaluable patients, or 21.5% for all patients entered in the studies. Of the 57 patients whose disease had progressed either during previous therapy or within 4 months of discontinuing previous therapy, 13 (23%) responded to docetaxel (EORTC data). Major adverse effects of docetaxel observed in approximately half the patients (particularly those who received more than four courses) included skin reactions and fluid retention. Grade III or IV neutropenia was common but short-lived. Severe acute hypersensitivity reactions occurred in approximately 5% of patients. Docetaxel now warrants evaluation as part of first-line therapy. Studies aimed at reducing the incidence of fluid retention and skin reactions with docetaxel are ongoing.
Adult↗
Recent advances in the application of gene therapy to human disease.
PURPOSE: To review the recent advances in the application of genetic modification strategies to the therapy of human diseases for which a molecular defect is known. METHODS: A computerized data bank search, the minutes of the National Institutes of Health (NIH) Recombinant DNA Advisory Committee published in the Federal Record, and reports of human clinical trials were used as data sources for this review. Clinical trials included in this review were published in the literature or approved by the NIH Recombinant DNA Advisory Committee. STUDY SELECTION: Evaluations of the efficacy of genetic modification strategies in clinical trials in human and in animal models are summarized. The design and outcome of the genetic modification strategies employed are reviewed for 16 marking trials, 16 gene replacement trials for molecular deficiency diseases, 3 chemoprotection and 4 chemotherapy sensitization trials, 11 cancer vaccine trials, 2 antisense oligonucleotide trials, and 3 molecular immunotherapy trials. DATA SYNTHESIS: The marking trials have shown that residual leukemia cells in the infused autologous marrow can contribute to relapse following autologous bone marrow transplants. The use of genetic modification for the replacement of missing or deficient genes in severe combined immunodeficiency, familial hypercholesterolemia, and cystic fibrosis has been associated with encouraging results so far. Clinical genetic therapy trials involving cancer vaccines, antisense oligonucleotides, adoptive immunotherapy with genetically modified T cells, delivery vectors containing interleukin-1 receptor inhibitor for arthritis, replacement strategies for storage diseases, and genetic suppression of human immunodeficiency viral replication are just commencing. CONCLUSIONS: The clinical application of genetic modification techniques has thus far been successful in the beginning phases of this field. These early results suggest that continuation of gene therapy trials designed to correct the molecular changes that lead to disease states in humans is warranted. Evaluation of such clinical trials in the future may be based on the analysis of assays for short-term surrogate endpoints, as well as on the therapeutic outcomes of the trial, such as survival or remission.
Bone Marrow Transplantation↗
Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer.
PURPOSE: To determine the activity of carboplatin in patients with ovarian cancer who progressed on taxane (paclitaxel or docetaxel) therapy. PATIENTS AND METHODS: Thirty-three patients with ovarian cancers refractory to platinum and taxane therapy were treated with single-agent carboplatin reinduction once the disease progressed on a taxane. The starting dose of carboplatin was 300 mg/m2 at 28-day intervals. RESULTS: Patients were a median age of 56 years (range, 31 to 80), had a median Zubrod performance status of 1 (range, 0 to 2) and had received a median of three prior chemotherapy regimens (range, two to eight) and one pretaxane platinum regimen (range, one to three). Twenty-six patients had a platinum-free interval of at least 12 months at the time of posttaxane re-treatment with carboplatin. There were seven of 33 (21%) partial responses, with a median duration of 7+ months (range, 2+ to 12+). Responses were noted only in patients with at least a 12-month platinum-free interval and an initial sensitivity to a taxane. The therapy was well tolerated and neurotoxicity was absent. CONCLUSION: A subset of patients with platinum-refractory disease that initially responded to a taxane and who eventually have a platinum-free interval of at least 1 year may respond to carboplatin reinduction. This finding may be secondary to paclitaxel or docetaxel therapy that leads to the reversal of platinum resistance, or the prolonged platinum-free interval permits the loss of resistance to platinum by the tumor. Carboplatin reinduction should be considered in the treatment of patients whose ovarian cancer progresses after an initial sensitivity to a taxane and who had a prolonged platinum-free interval.
Adult↗
Use of safety-modified retroviruses to introduce chemotherapy resistance sequences into normal hematopoietic cells for chemoprotection during the therapy of ovarian cancer: a pilot trial.
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Adolescent↗