Expression and subcellular localization of the cyclin-dependent kinase inhibitor p27(Kip1) in epithelial ovarian cancer.

OBJECTIVE: To determine if p27(Kip1) expression was altered in epithelial ovarian cancers as compared to normal ovarian surface epithelial (NOSE) cells and to determine if subcellular localization of p27(Kip1) was an important feature. METHODS: Thirteen tumor samples (1 Stage IC [early] and 12 Stage III/IV [advanced]) from patients with epithelial ovarian cancer and five NOSE samples were evaluated. Samples were surgically dissected to obtain an enriched population (90%) of cancer cells. The level of p27(Kip1) protein expression was determined by Western blot analysis. Actin was used as a loading control, and results were quantified by scanning densitometry using the ratio of the p27(Kip1) signal to the actin signal for comparison. To evaluate the subcellular localization of p27(Kip1), immunocytochemical staining was performed. Clinical pathological parameters were correlated to nuclear p27(Kip1) staining to establish if any association existed. RESULTS: When comparing the expression of p27(Kip1) between NOSE and ovarian cancer samples, only 2 of 13 ovarian cancer samples had altered p27(Kip1) expression. No correlation was found between the expression level of p27(Kip1) on Western blot and clinical pathological correlates. While no correlation between expression level of p27(Kip1) and subcellular localization was found, decreased nuclear staining (1+) was associated with shorter survivals using the log-rank test (P < 0.001). More importantly, in all tumor samples examined under the microscope, no nuclear p27(Kip1) staining was noted in cells that were undergoing mitosis. CONCLUSIONS: p27(Kip1) protein degradation may not be modified in ovarian cancer cells undergoing mitosis. Altered expression of p27(Kip1) is not an overwhelming feature in certain epithelial ovarian cancers. Decreased nuclear staining of p27(Kip1) is associated with poor survival in some epithelial ovarian cancers.

The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors.

Numerous chemotherapeutic agents have been shown to have an inhibitory effect on endothelial cell proliferation and migration, and tubule formation. In this study, we examined the antiangiogenic activity of docetaxel. Docetaxel inhibited endothelial cell proliferation and tubule formation in vitro in a dose-dependent fashion. Docetaxel treatment also inhibited angiogenesis in an in vivo Matrigel plug assay. The endothelial stimulating factors, vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor are able to protect endothelial cells from the antiangiogenic properties of docetaxel. This protective effect can be overcome by a recombinant humanized monoclonal antibody directed against VEGF in both in vitro and in vivo models. Similarly, combination of docetaxel with the antiangiogenic agent 2-methoxyestradiol also overcomes the protective effect of VEGF in both in vitro and in vivo models. These data suggest that microenvironmental factors (e.g., local release of VEGF and basic fibroblast growth factor) could play a role in decreasing the antiangiogenic effects of docetaxel, whereas agents such as 2- methoxyestradiol and recombinant humanized monoclonal antibody directed against VEGF may reverse this protective effect.

Spirometric pulmonary function in healthy preschool children.

The purpose of this study was to evaluate spirometric lung function in normal children ages 3 to 6 yr. Spirometric measurements were obtained at nursery and daycare centers by experienced pediatric pulmonary function technicians. Of 307 children recruited, 259 fulfilled our criteria as normal. Of these, 82.6% (214) were able to perform technically acceptable and reproducible maneuvers during a testing session limited to 15 min. The regression model with log-transformed parameters of pulmonary function and height had the best correlations. After accounting for height in the model, other physical traits and health questionnaire items did not contribute significantly. PEFR, FVC, FEV1, and FEF25-75 all increased with increasing height; correlation coefficients were 0.73, 0.93, 0.92, and 0.67, respectively. The group mean coefficients of variation for replicate measurements of PEFR, FVC, FEV1, and FEF25-75 were 7.8%, 2.5%, 2.7%, and 8.3%, respectively. There was a significant decrease in the ratio FEV1/FVC with increasing height; the mean predicted FEV1/FVC was 0.97 at 90 cm height and 0.89 at 125 cm height. In conclusion, reproducible spirometry can be obtained in the majority of preschool children and has the potential to improve our assessment and management of pulmonary disease.

A comparison of lower extremity muscle strength, obesity, and depression scores in elderly subjects with knee pain with and without radiographic evidence of knee osteoarthritis.

OBJECTIVE: To determine, in subjects with knee pain but no radiographic changes of tibiofemoral or patellofemoral compartment osteoarthritis (OA), whether mean body weight, quadriceps and hamstring strength, lower extremity muscle mass, depression scores, and perceptions of their general health status differed from those of subjects with symptomatic knee OA. METHODS: Subjects were 25 women and 10 men with knee pain and radiographic evidence of OA at the baseline examination, and 21 women and 16 men who had knee pain at the baseline examination but no radiographic evidence of knee OA at either baseline examination or followup evaluation performed, on average, 31 months later. These individuals were a subset of a cohort of 462 independently living elderly individuals recruited by telephone interview after random selection through random digit dialing of households in central Indiana. Data from an additional 134 subjects who had neither knee pain nor radiographic changes of OA at either the baseline or followup examination were analyzed for comparison. Lower extremity muscle strength was measured by isokinetic dynamometry, lean tissue (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry, depression by Center for Epidemiology Depression (CES-D) scale. knee pain by Western Ontario McMaster University OA instrument, and perceived general health status by the Medical Outcome Survey Short Form-36. RESULTS: In contrast to those with symptomatic knee OA, those who had knee pain but no radiographic evidence of OA were less obese, had hamstring as well as quadriceps weakness, and had CES-D scores high enough to qualify for a diagnosis of clinical depression. CONCLUSION: Among subjects with knee pain but no OA--and among women in this subset, in particular--knee pain may be a manifestation of depression. rather than of joint disease.

Immunohistochemistry can be used to subtype acute myeloid leukemia in routinely processed bone marrow biopsy specimens. Comparison with flow cytometry.

Flow cytometry (FC) is the preferred method of immunophenotyping acute myeloid leukemia (AML). However, there are situations in which FC is unavailable and in which immunohistologic staining of bone marrow biopsy specimens can be used to provide immunophenotypic information. To evaluate immunohistologic staining and to confirm its value, we selected 80 newly diagnosed cases of AML that were classified according to French-American-British (FAB) criteria and confirmed by flow cytometric analysis for this study. Paraffin-embedded bone marrow specimens were stained using a panel of antibodies that included CD34 (QBEND10), antimyeloperoxidase (anti-MPO), antihemoglobin, factor VIII-related antigen, and 3 epitopes of CD68 (HAM56, KP1, and PG-M1). Our findings suggest that with the use of the paraffin-reactive antibodies CD34 (QBEND10), MPO, CD68 (PG-M1), antihemoglobin, and factor VIII-related antigen, immunohistochemistry can be used to subclassify AML. Comparison of immunohistochemical results with FC immunophenotyping suggests that there is significant concordance in the results for markers that can be used with both techniques, indicating that the sensitivity and specificity of both methods is comparable (P > .53 in all cases).

Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The aim of this study was to determine the effects of independent prognostic variables, such as prechemotherapy tumor markers, the extent of disease at diagnosis, the tumor markers postchemotherapy (PC), and the pathology of the PC residual mass on the overall survival of patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT). METHODS: The authors undertook a retrospective review of 39 patients with PMNSGCT between 1983 and 1997 who received their initial chemotherapy at Indiana University and 36 additional patients referred for PC resection. All patients received chemotherapy based on the combination of cisplatin and etoposide. The median follow-up was 22 months (range, 12-144 months). RESULTS: The prechemotherapy tumor markers did not affect overall survival. Extent of disease (mediastinal only vs. visceral metastases) was an important prognostic factor for survival in univariate analysis (P = 0.042). Sixty-two of 75 patients underwent PC resection of residual disease. Fifteen of the 62 patients achieved a CR with chemotherapy alone, as the PC resection revealed only necrosis. Fourteen of these 15 patients continuously had no evidence of disease (NED). Forty-seven of the 62 patients had NED with chemotherapy and PC resection, including 31 with teratoma and 16 with carcinoma. However, 11 of 31 with teratoma and 11 of 16 with carcinoma subsequently relapsed. Although 18 patients had elevated tumor markers at the time of PC resection, 6 of 18 had only necrosis and 4 had teratoma. The PC tumor markers did not affect survival. The pathology of the resected specimen was the most significant predictor of survival in multivariate analysis (P < 0.001). CONCLUSIONS: Twenty-eight of 39 patients (71.8%) with PMNSGCT treated at Indiana University achieved NED status, but only 16 (41%) continuously had NED. Twenty of 36 (55.5%) referred for resection continuously had NED. Disease confined to the mediastinum and necrosis in the PC specimen were important prognostic factors for survival.

Cyclooxygenase-2 expression in human pancreatic adenocarcinomas.

Cyclooxygenase-2 (COX-2) expression is up-regulated in several types of human cancers and has also been directly linked to carcinogenesis. To investigate the role of COX-2 in pancreatic cancer, we evaluated COX-2 protein expression in primary human pancreatic adenocarcinomas (n = 23) and matched normal adjacent tissue (n = 11) by immunoblot analysis. COX-2 expression was found to be significantly elevated in the pancreatic tumor specimens compared with normal pancreatic tissue. To examine whether the elevated levels of COX-2 protein observed in pancreatic tumors correlated with the presence of oncogenic K-ras, we determined the K-ras mutation status in a subset of the tumors and corresponding normal tissues. The presence of oncogenic K-ras did not correlate with the level of COX-2 protein expressed in the pancreatic adenocarcinomas analyzed. These observations were also confirmed in a panel of human pancreatic tumor cell lines. Furthermore, in the pancreatic tumor cell line expressing the highest level of COX-2 (BxPC-3), COX-2 expression was demonstrated to be independent of Erk1/2 activation. The lack of correlation between COX-2 and oncogenic K-ras expression suggests that Ras activation may not be sufficient to induce COX-2 expression in pancreatic tumor cells and that the aberrant activation of signaling pathways other than Ras may be required for up-regulating COX-2 expression. We also report that the COX inhibitors sulindac, indomethacin and NS-398 inhibit cell growth in both COX-2-positive (BxPC-3) and COX-2-negative (PaCa-2) pancreatic tumor cell lines. However, suppression of cell growth by indomethacin and NS-398 was significantly greater in the BxPC-3 cell line compared with the PaCa-2 cell line (P = 0.004 and P < 0.001, respectively). In addition, the three COX inhibitors reduce prostaglandin E(2) levels in the BxPC-3 cell line. Taken together, our data suggest that COX-2 may play an important role in pancreatic tumorigenesis and therefore be a promising chemotherapeutic target for the treatment of pancreatic cancer.

Results and outcome of retroperitoneal lymph node dissection for clinical stage I embryonal carcinoma--predominant testis cancer.

PURPOSE: To determine the incidence of metastatic disease and usage of chemotherapy (adjuvant or metastatic) after primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I embryonal carcinoma (EC)-predominant testicular cancer. EC predominance was defined as the presence of EC at a level greater than that of any other histologic diagnosis. PATIENTS AND METHODS: All CS I patients with nonseminomatous germ cell tumors who underwent RPLND at Indiana University from 1990 to 1995 were reviewed retrospectively. RESULTS: Two-year follow-up was available for 292 of 320 patients. EC-predominant disease was found in 125 (42.8%) of 292. Eighty-five (68.0%) of 125 patients with EC-predominant disease had pathologic stage (PS) I, and 18 (21.2%) of this group of 85 relapsed. A significantly lower PS I relapse rate of 3% was found for patients who had non-EC-predominant disease (P <.0001). PS II disease was more frequent in patients with EC predominance, as 40 (32.0%) of 125 had retroperitoneal metastases, compared with 26 (15.6%) of 167 patients with a non-EC-predominant histologic diagnosis (P =.0024). Chemotherapy was administered to 48 (38.4%) of the 125 patients with CS I EC-predominant disease after RPLND. This included 25 CS I patients with PS II disease who received adjuvant chemotherapy in addition to 23 patients who subsequently required chemotherapy for relapse after RPLND. Ten (66. 6%) of 15 PS II EC-predominant patients were cured by surgery alone. Currently, all 125 EC-predominant patients are disease-free. CONCLUSION: Patients with CS I EC-predominant disease are at a relatively high risk for metastatic disease.

Quadriceps strength in women with radiographically progressive osteoarthritis of the knee and those with stable radiographic changes.

OBJECTIVE: To explore the relationship between lower extremity weakness and the progression of established radiographic changes of knee osteoarthritis (OA). METHODS: The study cohort of 342 elderly subjects was recruited from central Indiana by random digit dialing. We analyzed 79 subjects who had definite radiographic changes of unilateral or bilateral knee OA at baseline and for whom baseline data for lower extremity muscle strength and lean tissue mass and baseline and followup assessments of knee pain were available. Radiographs were graded for severity of OA at baseline and again about 2.5 years later (mean 31.5 months). Knee pain was evaluated at the same examination. Strength of the knee flexors and extensors was assessed bilaterally at baseline by isokinetic dynamometry and lower extremity muscle mass by dual energy x-ray absorptiometry. RESULTS: Mean peak knee extensor strength of women with progressive OA, before and after adjustment for lower extremity muscle mass, was about 9% lower than that in those with stable radiographic changes, but this difference was not statistically significant. No difference was apparent between the 2 groups with respect to knee flexor (hamstring) strength. The decrease in quadriceps strength among women with progressive OA, relative to those with stable OA, did not appear to be attributable to knee pain, and knee extensor strength at baseline bore no apparent relationship to the development or progression of knee pain among those with OA. CONCLUSION: We have shown previously that quadriceps weakness may be of etiologic importance in development of knee OA. The absence of a significant difference in quadriceps strength between subjects with radiographically stable OA and those whose joint damage progressed suggests that factors other than quadriceps weakness are more important determinants of OA progression.

Reliability, validity, and application of the medical outcomes study 36-item short-form health survey (SF-36) in schizophrenic patients treated with olanzapine versus haloperidol.

UNLABELLED: Schizophrenia leads to impairments in mental, social, and physical functioning, which should be included in evaluations of treatment. OBJECTIVES: This study was designed to determine the reliability and validity of the Medical Outcomes Study Short Form Health Survey (SF-36) for schizophrenic patients, to characterize perceived functioning and well being and to compare short-term change in SF-36 scores for patients treated with olanzapine or haloperidol. RESEARCH DESIGN: Data were obtained from a randomized, double-blind trial comparing these agents for safety, efficacy, and cost effectiveness. A 6-week acute treatment portion preceded a 46-week "responder extension" phase. SUBJECTS: A subsample (n = 1,155) completing a pre-treatment SF-36 provided data for this study. MEASURES: Psychometric analyses were conducted, and perceived level of functioning was compared with that for the US adult population. Change from baseline to 6 weeks was examined by treatment group. RESULTS: Clear evidence was obtained for the instrument's reliability and validity for these patients. There were marked deficits in General health, Vitality, Mental health, Social functioning, and in Role limitations resulting from both physical and emotional problems. Olanzapine-treated patients improved in 5 of 8 domains to a significantly greater degree than did haloperidol patients. CONCLUSIONS: The SF-36 can be a reliable and valid measure of perceived functioning and well being for schizophrenic patients. The perceptions of functioning can be valuable indices of disease burden and can help to demonstrate the effectiveness of newer antipsychotic medications such as olanzapine.

Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas.

BACKGROUND: The regimen of procarbazine, CCNU, and vincristine is active against gliomas. Previous attempts at dose-intensification have been unsuccessful because of delayed and cumulative myelosuppression. We sought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose-escalation and time compression. PROCEDURE: Eleven patients, age 2.8-35.9 years, with newly diagnosed (n = 10) or recurrent (n = 1) gliomas underwent PBSC harvesting after mobilization with G-CSF. Chemotherapy consisted of CCNU 130 mg/m2 on day 0, vincristine 1.5 mg/m2 on days 0 and 7, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered 28 days apart or when counts recovered. Involved field radiation was administered to newly diagnosed high-grade glioma patients following recovery from chemotherapy. RESULTS: Compared to the standard PCV regimen given every 6 weeks, dose intensity received was 1.7- and 1.8-fold greater for CCNU and procarbazine. Chemotherapy was delivered on time in 33/41 (80.5%) courses. Four courses (9.8%) were complicated by absolute neutrophil counts < 200/microL; platelet nadirs < 50,000/microL occurred in two courses (4.9%). Fever with neutropenia complicated three courses. Eight of 9 patients with measurable disease had an objective decrease in tumor size and/or decreased enhancement. Median survival for patients with high-grade gliomas (n = 6) was 13 months. CONCLUSIONS: Dose-intensification of PCV is possible using PBSCs.

Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women?

OBJECTIVE: To determine whether baseline lower extremity muscle weakness is a risk factor for incident radiographic osteoarthritis (OA) of the knee. METHODS: This prospective study involved 342 elderly community-dwelling subjects (178 women, 164 men) from central Indiana, for whom baseline and followup (mean interval 31.3 months) knee radiographs were available. Lower extremity muscle strength was measured by isokinetic dynamometry and lean tissue (i.e., muscle) mass in the lower extremities by dual x-ray absorptiometry. RESULTS: Knee OA was associated with an increase in body weight in women (P = 0.0014), but not in men. In both sexes, lower extremity muscle mass exhibited a strong positive correlation with body weight. In women, after adjustment for body weight, knee extensor strength was 18% lower at baseline among subjects who developed incident knee OA than among the controls (P = 0.053), whereas after adjustment for lower extremity muscle mass, knee extensor strength was 15% lower than in the controls (P not significant). In men, in contrast, adjusted knee extensor strength at baseline was comparable to that in the controls. Among the 13 women who developed incident OA, there was a strong, highly significant negative correlation between body weight and extensor strength (r = -0.740, P = 0.003), that is, the more obese the subject, the greater the reduction of quadriceps strength. In contrast, among the 14 men who developed incident OA, a modest positive correlation existed between weight and quadriceps strength (r = 0.455, P = 0.058). No correlation between knee flexor (hamstring) strength and knee OA was seen in either sex. CONCLUSION: Reduced quadriceps strength relative to body weight may be a risk factor for knee OA in women.

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUND: In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS: We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS: In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS: Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Quadriceps weakness and osteoarthritis of the knee.

BACKGROUND: The quadriceps weakness commonly associated with osteoarthritis of the knee is widely believed to result from disuse atrophy secondary to pain in the involved joint. However, quadriceps weakness may be an etiologic factor in the development of osteoarthritis. OBJECTIVE: To explore the relation between lower-extremity weakness and osteoarthritis of the knee. DESIGN: Cross-sectional prevalence study. SETTING: Population-based, with recruitment by random-digit dialing. PARTICIPANTS: 462 volunteers 65 years of age or older. MEASUREMENTS: Radiographs of the knee were graded for the presence of osteoarthritis. Knee pain and function were assessed with the Western Ontario and McMaster Universities Arthritis Index, the strength of leg flexors and extensors was assessed with isokinetic dynamometry, and lower-extremity lean tissue mass was assessed with dual-energy x-ray absorptiometry. RESULTS: Among participants with osteoarthritis, quadriceps weakness, but not hamstring weakness, was common. The ratio of extensor strength to body weight was approximately 20% lower in those with than in those without radiographic osteoarthritis. Notably, among women with tibiofemoral osteoarthritis, extensor weakness was present in the absence of knee pain and was seen in participants with normal lower-extremity lean mass (extensor strength, 30.1 lb-ft for those with osteoarthritis and 34.8 lb-ft for those without osteoarthritis; P < 0.001). After adjustment for body weight, age, and sex, lesser quadriceps strength remained predictive of both radiographic and symptomatic osteoarthritis of the knee (odds ratio for prevalence of osteoarthritis per 10 lb-ft loss of strength, 0.8 [95% CI, 0.71 to 0.90] for radiographic osteoarthritis and 0.71 [CI, 0.51 to 0.87] for symptomatic osteoarthritis). CONCLUSION: Quadriceps weakness may be present in patients who have osteoarthritis but do not have knee pain or muscle atrophy; this suggests that the weakness may be due to muscle dysfunction. The data are consistent with the possibility that quadriceps weakness is a primary risk factor for knee pain, disability, and progression of joint damage in persons with osteoarthritis of the knee.

Decision analysis for avoiding postchemotherapy surgery in patients with disseminated nonseminomatous germ cell tumors.

PURPOSE: This retrospective study was undertaken to assess the outcome of patients with disseminated nonseminomatous germ cell tumor (NSGCT) managed under a postchemotherapy strategy developed at Indiana University. PATIENTS AND METHODS: This is a retrospective analysis of 295 consecutive patients with disseminated NSGCT treated with primary chemotherapy at Indiana University from 1987 to 1994. The patients were placed into five groups based on response to primary chemotherapy and the presence or absence of teratoma in the primary tumor. The 295 patients were divided as follows: group A (complete remission [CR]) n = 78; group B (unresectable), n = 50; group C (serologic CR, teratoma-positive primary tumor, resectable partial remission [PR]), n = 90; group D [serologic CR, teratoma-negative primary tumor, < 90% radiographic PR], n = 50; and group E (serologic CR, teratoma-negative primary tumor, > or = 90% radiographic PR), n = 27. Groups A, B, and E patients were routinely observed after chemotherapy, whereas groups C and D patients were routinely taken to postchemotherapy surgery. RESULTS: The percent of patients who continuously had no evidence of disease (NED) were as follows: group A, 92%; group B, 40%; group C, 87%; group D, 86%; and group E, 74%. In assessing group A patients, the bulk of retroperitoneal disease at presentation had no influence on ultimate outcome. CONCLUSION: Patients with NSGCT who achieve a serologic and radiographic CR with primary chemotherapy (group A) can be safely observed without surgical intervention, regardless of initial tumor bulk. Patients with a teratoma-negative primary tumor who achieve a serologic CR and a > or = 90% radiographic remission and are followed-up without surgical resection (group E) are at an increased risk of relapsed NSGCT. Decisions about postchemotherapy resection in this group remain complicated and controversial. Options include observation with serial radiologic evaluation or surgical resection of persistent mass or masses.

Cord blood mononuclear cell transformation assay for screening for the presence of Epstein-Barr virus.

EBV-induced lymphoproliferative disease (EBV-LPD) is a serious and potentially fatal complication following stem cell transplantation. Strategies have been developed for the cultivation of donor-derived, EBV-specific cytotoxic T lymphocytes (CTL) for stem cell transplant (SCT) patients affected with these disorders, using donor-derived, EBV-transformed B lymphoblastoid cell lines (BLCL) as stimulators. Although cultivation of EBV-transformed BLCL is possible without using an exogenous source of EBV, transformation of autologous B cells with endogenous virus may be slow and inconsistent. Therefore, if exogenous strains of EBV are used to generate BLCL, it may be beneficial to patients to ensure that these cell lines are not producing virus that potentially could be conveyed at the time of CTL infusion. A reliable method of screening for EBV using a cord blood transformation assay has been developed and is described.

A prospective, controlled study showing that rubber gloves are the major contributor to latex aeroallergen levels in the operating room.

BACKGROUND: Although protocols have been published for reducing natural rubber latex exposure in medical environments, there are no objective data documenting their effectiveness. OBJECTIVE: We prospectively studied the impact of a single intervention, substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves, on latex aeroallergen levels in a single operating room (OR). METHODS: We sampled OR air on 52 consecutive days, including 33 surgery days and 19 nonsurgery days. On each surgery day all personnel wore either high-allergen gloves (n = 18 days) or low-allergen gloves (n = 15 days). Latex aeroallergen levels (in nanograms per cubic meter) and extractable latex glove allergen contents (in allergen units per milliliter) were measured by inhibition immunoassays. An on-site study monitor recorded the number of gloves used, the total time spent by all patients in the OR each day (OR time), and the total time of all procedures for each day (operating procedure time). RESULTS: Latex aeroallergen levels during low-allergen glove use days (mean, 1.1 ng/m3; median, 0.9 ng/m3; range, 0.1 to 3.5 ng/m3) were significantly lower than on high-allergen glove use days (mean, 13.7 ng/m3; median, 7.7 ng/m3; range, 2.2 to 56.4 ng/m3) (p < 0.001) but not significantly different from that on nonsurgery days (mean, 0.6 ng/m3; median, 0.3 ng/m3; range, 0.1 to 3.6 ng/m3). Latex aeroallergen levels were strongly correlated with the total number of gloves used on designated high-allergen glove days (r = 0.66, p = 0.003). There was no appreciable day-to-day carryover of latex aeroallergen. CONCLUSIONS: The substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves can reduce levels of latex aeroallergen by more than 10-fold in an OR environment.

Prospective study of extractable latex allergen contents of disposable medical gloves.

BACKGROUND: Exposure to natural rubber latex medical gloves poses risks to latex-sensitive patients and medical workers. Preliminary studies have shown that the latex allergen contents of these gloves vary widely. OBJECTIVE: To study long-term trends in latex allergen levels of disposable medical gloves prospectively, and to identify lower allergen gloves for purchase by our medical center. METHODS: Extractable total latex allergen was measured by solid-phase inhibition immunoassay. Allergen contents of gloves were expressed in allergy units (AU)/mL relative to a raw latex standard assigned an arbitrary potency of 100,000 AU/mL. RESULTS: For gloves in use during July, 1993, extractable allergen levels ranged from < 10 to 5,500 AU/mL among nine lots of examination gloves, from < 10 to 2,300 AU/mL among 13 lots of surgical gloves, and from < 10 to 1,000 AU/mL among five lots of chemotherapy, autopsy, or utility gloves. Among ten lots of examination gloves purchased on two occasions between July, 1993 and January, 1994, the allergen levels in two of the three private label brands were more variable (6- to 40-fold) than in the other eight brands tested (0- to 2-fold). CONCLUSIONS: Extractable allergen levels in latex medical gloves remain highly variable, particularly among some private label brands. Use of synthetic gloves or lower allergen latex gloves should lessen exposure of latex-sensitized patients and health care workers to latex aeroallergens.