The Gynecologic Cancer Intergroup (GCIG): history and current status.
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Biomedical subjects
Publications and source records attributed to M Bacon.
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Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.
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BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.
AIM: to describe the technical, diagnostic and logistical problems encountered in a syncope and falls clinic in a district general hospital. METHODS: we have reviewed 157 consecutive patients and the problems encountered in their assessment at the clinic. RESULTS: 143 patients (91%) completed assessment, which included head-up tilt and carotid sinus massage. We reached a diagnosis in 75 of these (52%). Difficulties with continuous blood pressure monitoring caused testing to be abandoned in four cases and caused considerable delay (up to 30 min) in 45% of the rest. Eight patients (5%) refused consent for carotid sinus massage and two others had neurological sequelae. Some patients fulfilled diagnostic criteria on testing but remained asymptomatic, making an attributable diagnosis difficult. This was most noticeable with vasodepressor carotid sinus hypersensitivity. The limited facilities in a district general hospital and the time-consuming nature of the testing resulted in a considerable delay between referral and assessment (58 days +/- 25.9), which may adversely affect diagnostic yield. CONCLUSIONS: syncope clinics have a role in the assessment of elderly people with recurrent syncope and unexplained falls. Enthusiasm for this approach has to be tempered with an awareness of the limitations of the tests involved and an appreciation of the logistical problems likely to be encountered in a district hospital.
Both environmental and genetic factors appear to contribute to the risk for suicide. The serotonergic system has been implicated in depression, impulsivity and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Suicide has been associated with polymorphisms in intron 7 of the TPH gene. These alleles were studied in samples from 47 deceased Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment spanning the region of interest was amplified. The A218C polymorphism was visualized by restriction fragment length polymorphism (RFLP) and the A779C was sequenced. Neither A218C nor A779C appeared to be associated with suicide in this population. These results did not change when the sample was stratified by age (10-21 years, 22-31 years) or when violent suicides were selected. The complexity of the phenotype of suicide may reflect multiple biological and social etiologic factors, and poses a worthy challenge for genetic studies.
The ProP protein of Escherichia coli is an osmoregulatory H+-compatible solute cotransporter. ProP is activated by an osmotic upshift in both whole cells and membrane vesicles. We are using biochemical and biophysical techniques to explore the osmosensory and catalytic mechanisms of ProP. We now report the purification and reconstitution of the active transporter. Protein purification was facilitated by the addition of six histidine (His) codons to the 3' end of proP. The recombinant gene was overexpressed from the E. coli galP promoter, and ProP-(His)6 was shown to be functionally equivalent to wild-type ProP by enzymatic assay of whole cells. ProP-(His)6, purified by Ni2+ (NTA) affinity chromatography, cross-reacted with antibodies raised against the ProP protein. ProP-(His)6 was reconstituted into Triton X-100 destabilized liposomes prepared with E. coli phospholipid. The reconstituted transporter mediated proline accumulation only if (1) a membrane potential was generated by valinomycin-mediated K+ efflux and (2) the proteoliposomes were subjected to an osmotic upshift (0.6 M sucrose). Activity was also stimulated by DeltapH. Pure ProP acts, in the proteoliposome environment, as sensor, transducer, and respondent to a hyperosmotic shift. It is the first such osmosensor to be isolated.
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This paper describes a monoclonal antibody (mAb), anti-pig CD45 (MAC323), that is directed against a polymorphic determinant. A monomorphic anti-pig CD45 mAb (K252.1E4) bound strongly to leucocytes from both MAC323+ and MAC323- pigs, demonstrating the absence of the epitope rather than the CD45 molecule. The MAC323 determinant was present on all leucocytes in positive pigs, exhibiting different expression levels on subsets (monocytes > lymphocytes > polymorphs), but was absent on red blood cells. Pigs lacking this determinant were healthy and grew normally. Careful selection of male and female SLAb/b pigs produced families that were either positive or negative for this epitope. Interbreeding within these families identified the genetic segregation of this variation, which is consistent with the CD45(323) epitope being inherited as a simple dominant autosomal gene. The lack of this determinant in certain lines of inbred pigs has been used to study the homing, lifespan and tissue distribution of donor unlabelled MAC323+ leucocytes and their subsets (using single- and two-colour immunocytological techniques) in MAC323- recipients after either intravenous injection or exchange transfusion. These results, identifying trafficking areas and subsets in constitutive lymphoid and inflammatory tissues, obtained using this genetic marker, extend those obtained previously using fluorescein isothiocyanate (FITC)-labelled donor cells.
This study examines oropharyngeal swallow disorders and measures of pharyngeal and laryngeal movement during deglutition from videofluorographic studies of oropharyngeal swallow in 9 patients who had undergone supraglottic laryngectomy and 9 age-matched normal subjects. The swallows of surgical patients were examined at 2 weeks and 3 months postoperatively. Two critical factors in recovery of swallowing were identified: (a) airway closure at the laryngeal entrance, that is, the space between the arytenoid cartilage and the base of the tongue, and (b) the movement of the tongue base to make complete contact with the posterior pharyngeal wall. When patients achieved these two functions, they returned to normal swallowing. The duration of tongue base contact to the posterior pharyngeal wall and extent of anterior movement of the arytenoid increased significantly from 2 weeks to 3 months in the surgical patients. At 2 weeks postsurgery, patients who had undergone supraglottic laryngectomy exhibited significantly shorter airway closure and tongue base to pharyngeal wall contact, reduced laryngeal elevation, increased width of cricopharyngeal (CP) opening, and later onset of airway closure and tongue base movement than normal subjects. These significant differences remained at 3 months postoperatively, although swallow measures were moving toward normal in the patients who had undergone supraglottic laryngectomy. Comparison of patients not eating at 2 weeks with patients at the time of first eating revealed significantly longer duration of tongue base contact to the pharyngeal wall, longer duration of airway closure, and greater movement of the arytenoid in patients who were eating. Results indicate that the focus of swallowing therapy after supraglottic laryngectomy should be on improvement of posterior movement of the tongue base and anterior tilting of the arytenoid to close the airway entrance and improve bolus propulsion (in the case of the tongue base).
The bacterial quinol oxidase, cytochrome o, is an enzyme which is highly analogous to the better known cytochrome c oxidase, cytochrome aa3, but with the important difference that it lacks the near infra-red absorbing pigment CuA. In this article we report an absorption band in the near IR spectrum of cytochrome o with a maximal absorption at 758 nm, and which is attributable to the ferrous high-spin haem. The 758 nm band has an extinction coefficient of 0.2-0.3 mM-1.cm-1 at 758-800 nm. This region in cytochrome aa3 is dominated by the CuA absorption. The 758 nm absorption is lost on addition of CO or cyanide to the reduced enzyme. The carbon monoxide compound of cytochrome o also has absorbance bands in the near infra-red, and these may be attributable to a low-spin ferrous haem compound.
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2,183 employees from 13 Irish industries volunteered to take part in a risk factor identification and health counselling programme. Data are presented about the risk factor profile of the group. Alcohol abuse, overweight and hyperlipidaemia were prevalent, particularly among men. Hypertension, although relatively infrequent, was commoner among men and, like hyperlipidaemia and obesity, increased significantly with age. The subjects who smoked cigarettes accounted for 33% of the population studied, while 21% were ex-smokers, with substantially more ex-smokers among men than women. Only 22% of subjects took adequate exercise. Work stress was unusual but personal stress common. Only 75% of subjects used their seat belts regularly and the majority received no regular dental care. The role of industrial health programmes in disease prevention and health education, and in providing benefit to industry, is examined. Recommendations are made about effective means of encouraging healthy living in an industrial environment.
Three young women volunteers were trained through instructional feedback in two breathing procedures: diaphragmatic, derived from Eastern meditative techniques, and thoracic, involving opposite maneuvers. A single-subject reversal design was employed. Physiograph recordings of diaphragmatic expansion and mouth breathing provided the basis for feedback. Peripheral (digital) temperature was time-sampled at 1-min intervals and linear regression lines were fitted to the data. Temperature decreased throughout "normal" (baseline) breathing, probably due to warm outdoor and cool indoor temperatures. For two subjects, temperature during diaphragmatic breathing was generally stable; temperature during thoracic breathing showed significant decreases and did not differ from normal breathing. Within-session reversals showed dramatic changes in temperature as a function of breathing technique, which were maintained at follow-up, for these subjects. Temperature was more labile and decreased regardless of breathing procedure for the third subject. These data support a relationship between respiratory and vasomotor activity, and suggest that breathing strategy may be an uncontrolled variable in temperature biofeedback. It is further suggested that diaphragmatic breathing may facilitate temperature biofeedback or other types of relaxation training.