Strength and body composition changes in recreationally strength-trained individuals: comparison of one versus three sets resistance-training programmes.

PURPOSE: The purpose of this study was to determine the effects of increasing the volume of weight-training from one to three sets upon body composition and muscular strength. METHODS: Sixteen male weight-trainers volunteered to act as subjects and were randomly assigned to one of two training groups. Supervised weight-training targeting the upper body was conducted three times per week for eight weeks using one set (n = 8) or three sets (n = 8) of six repetitions to fatigue. Subjects were measured before and after the training intervention for (1) strength performance (N and kg) and (2) adiposity (sum of seven skinfold thicknesses in mm). RESULTS: Both training groups improved significantly (20.7%) in terms of muscular strength (P < 0.05) with no differences being observed between the one set (21.98% increase) and three set group (20.71% increase) after the training interventions (P > 0.05). Significant decreases were also observed for skinfold measures in the one set group (P < 0.05). CONCLUSIONS: One set of high intensity resistance training was as effective as three sets for increasing the strength of muscle groups in the upper body. The one set protocol also produced significantly greater decreases in adiposity.

Pegfilgrastim for the prevention of febrile neutropenia in patients with epithelial ovarian carcinoma--a cost-effectiveness analysis.

The objective is to assess the cost-effectiveness of pegfilgrastim for the prevention of hospitalization due to febrile neutropenia (FN) in patients with epithelial ovarian carcinoma (EOC) receiving taxane/platinum-based chemotherapy. A decision analysis model evaluated a hypothetical cohort of 10,000 patients receiving six cycles of taxane/platinum-based chemotherapy for EOC. Three strategies were analyzed for the prevention of hospitalization due to FN: 1) dose modifications and delays after a hospitalization for FN without the use of granulocyte-colony stimulating factors (G-CSF) (NO G-CSF); 2) all patients receive G-CSF with each chemotherapy cycle (1 degrees PROPHYLAXIS); 3) patients receive G-CSF for all subsequent chemotherapy cycles after a hospitalization for FN (2 degrees PROPHYLAXIS). The model was applied to two patient populations: 1) an average-risk population (FN hospitalization rate = 5%); 2) a high-risk population (FN hospitalization rate = 16%). Using baseline assumptions in an average-risk population, NO G-CSF was the least expensive strategy with a cost of $68 million and resulted in 2,860 hospitalizations for FN. 2 degrees PROPHYLAXIS resulted in 141 fewer hospitalizations than NO G-CSF at a cost of $76,288 per hospitalization prevented. 1 degrees PROPHYLAXIS was the most effective and resulted in 1,689 fewer hospitalizations for FN compared to NO G-CSF at a cost of $47,343 per hospitalization prevented. When this model is applied to a high-risk patient population, 1 degrees PROPHYLAXIS is more effective and less expensive than both NO G-CSF and 2 degrees PROPHYLAXIS. We conclude that in average-risk patients receiving chemotherapy for EOC the use of pegfilgrastim is effective at reducing hospitalizations due to FN, but at a significant cost. However, in high-risk patients, primary prophylaxis is the only cost-effective strategy and should be strongly considered.

Outcomes for patients with fallopian tube carcinoma managed with adjuvant chemotherapy following primary surgery: a retrospective university experience.

The aim is to evaluate disease-free (DFS) and overall survival (OS) of patients with fallopian tube carcinoma (FTCA) treated with adjuvant chemotherapy. An Institutional Review Board approved retrospective review identified 38 patients with FTCA that received adjuvant chemotherapy following primary surgery from 1975 to 2001. Median age was 56 (range 36-78) and 95% of patients were white. Twenty patients (53%) had FIGO stage III/IV FTCA. Seventeen patients underwent second-look laparotomy, 8 (47%) patients were found to have disease. Adjuvant chemotherapeutic regimens consisted of melphalan in 11 patients, platinum-based chemotherapy without paclitaxel in 17 patients, and the combination of paclitaxel and platinum in 10 patients. Although DFS was similar for the three chemotherapy cohorts (P= 0.19), patients receiving paclitaxel had superior OS compared to patients receiving either melphalan (P= 0.02) or platinum without paclitaxel (P= 0.04). Of the twenty patients with stage III/IV disease, 55% of patients had optimal cytoreduction performed at their initial surgery. Both median DFS, 68 versus 50 months (P= 0.14) and OS, 73 versus 50 months (P= 0.12) were greater in patients with optimal cytoreduction. When compared to historical chemotherapeutic regimens, the combination of paclitaxel and platinum has superior efficacy for the management of patients with FTCA. Although not statistically significant in our study, optimal cytoreduction likely improves both DFS and OS and should be the goal of all patients surgically managed for FTCA.

Intraperitoneal radioimmunochemotherapy of ovarian cancer: a phase I study.

A phase I trial was designed to examine the feasibility of combining interferon and Taxol with intraperitoneal radioimmunotherapy (177Lu-CC49). Patients with recurrent or persistent ovarian cancer confined to the abdominal cavity after first line therapy, Karnofsky performance status > 60, adequate liver, renal and hematologic function, and tumor that reacted with CC49 antibody were enrolled. Human recombinant alpha interferon (IFN) was administered as 4 subcutaneous injections of 3 x 10(6) U on alternate days beginning 5 days before RIT to increase the expression of the tumor-associated antigen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m2 compared to 177Lu-CC49 alone (45 mCi/m2). Taxol, which has radiosensitizing effects as well as antitumor activity against ovarian cancer, was given intraperitoneally (i.p.) 48 hrs before RIT. It was initiated at 25 mg/m2 and escalated at 25 mg/m2 increments to 100 mg/m2. Subsequent groups of patients were treated with IFN + 100 mg/m2 Taxol + escalating doses of 177Lu-CC49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for 177Lu-CC49 was 40 mCi/m2 when given with IFN + 100 mg/m2 Taxol. Interferon increased the effective whole body half-time of radioactivity and the whole body radiation dose. Taxol did not have a significant effect on pharmacokinetic or dosimetry parameters. Four of 17 patients with CT measurable disease had a partial response (PR) and 4 of 27 patients with non-measurable disease have progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m2) with RIT using 177Lu-CC49 and interferon was well tolerated, with bone marrow suppression as the dose-limiting toxicity.

Endometrial carcinoma.

Endometrial cancer is a common tumor of the female genital tract. The majority of women diagnosed with endometrial cancer present with early-stage disease. Although the optimal treatment for these patients requires hysterectomy, the use of lymphadenectomy is controversial. Growing scientific data support the use of lymphadenectomy in all patients diagnosed with endometrial cancer. When performed by an experienced surgeon, pelvic and para-aortic lymphadenectomy is a safe and potentially therapeutic procedure that provides prognostic information to the patient and physician. This information allows appropriate, cost-effective treatment strategies to be created for all women with endometrial cancer.

A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.

OBJECTIVE: The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. METHODS: Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy. RESULTS: Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). CONCLUSION: The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.

Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group Study.

From October 1995 to March 1997, a phase II trial of topotecan was carried out in chemotherapy-naive women with advanced, persistent, or recurrent uterine leiomyosarcomas. Thirty-six patients were entered. Median age was 53 years. Performance status was 0 (50%) in 18, 1 (36%) in 13, and 2 (14%) in 5. Most patients, 33 (92%), had undergone prior surgery, and 8 (22%) prior radiation therapy. Topotecan, 1.5 mg/m2. was administered intravenously daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. Patients received 1 to 13 courses with a median of 3 courses. The most frequent grade 4 adverse effects were neutropenia in 28 (78%), leukopenia in 8 (22%), thrombocytopenia in 3 (8%), and anemia in 3 (8%). Complete response was seen in 1 (3%), partial response in 3 (8%), stable disease in 12 (33%), and increasing tumor in 20 (56%). Thus topotecan at this dose and schedule does not appear to have major activity in uterine leiomyosarcomas.

Carcinosarcoma of the uterus associated with a nongestational choriocarcinoma.

Choriocarcinoma has been reported in association with endometrial carcinoma and as a metaplastic change in multiple carcinomas, including liver, urinary bladder, lung, and the gastrointestinal tract. We report choriocarcinoma in conjunction with a carcinosarcoma (also called malignant müllerian mixed tumor) in a 71-year-old woman whose hysterectomy specimen revealed two polypoid lesions of the endometrium, one arising from the anterior endometrium and one arising from the posterior endometrium. Histologic examination revealed three histologic patterns. The anterior endometrial lesion showed a FIGO grade 2 endometrioid endometrial adenocarcinoma. The posterior endometrial lesion showed a carcinosarcoma composed of a high-grade adenocarcinoma and scant homologous stromal sarcoma. In addition, a choriocarcinoma was identified intermixed with the adenocarcinoma. The syncytiocytotrophoblasts and cytotrophoblasts stained strongly with 0 human chorionic gonadotropin (beta-hCG) and human placental lactogen (hPL). The patient's beta-hCG levels on postoperative days 14, 27, and 42 were 283, 32, and 7 mIU/mL, respectively. This unusual case suggests the importance of identifying the choriocarcinomatous component, since the serum beta-hCG can serve as a marker of tumor recurrence postoperatively.

Complete surgical staging of early endometrial adenocarcinoma: optimizing patient outcomes.

Endometrial adenocarcinoma is the most common gynecologic malignancy. Strategies for treatment of this disease should not only emphasize quality of care resulting in cure of disease, but also use health care resources in the most efficient manner possible. Based on available data, we recommend that all patients with the diagnosis of endometrial carcinoma undergo complete surgical staging with lymph node dissection. Radiation therapy is reserved only for patients with evidence of extrauterine disease. This approach maximizes the amount of information available for treatment planning and offers the potential therapeutic advantage of lymph node dissection. Additionally, in a cost analysis, this approach appears to be the most cost-effective.

A comparison of treatment strategies for endometrial adenocarcinoma: analysis of financial impact.

OBJECTIVE: The aim of this study was to investigate the influence of three treatment strategies for adenocarcinoma of the endometrium on the utilization of adjuvant radiation therapy and the medical charges associated with each pattern of practice. METHODS: Three clinical algorithms felt to represent practice patterns for patients with endometrial cancer were considered: (1) comprehensive surgical staging of all patients, with adjuvant pelvic radiation reserved for documented cases of extrauterine disease, (2) total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) with lymph node dissection reserved for cases of myometrial invasion, followed by adjuvant radiation based on the presence of uterine risk factors, and (3) TAH/BSO followed by intraoperative pathologic assessment of the uterus and consultation with a "surgical" oncologist for comprehensive staging. Each algorithm was applied to a cohort of 190 surgically staged patients identified through a retrospective medical records review. The use of radiation in each algorithm was quantified and the associated financial impact was estimated using hospital charges. RESULTS: Treatment algorithm 1 yielded the lowest charges per patient at $12,778.52. Treatment algorithms 2 and 3 had associated charges per patient of $15,997.02 and $17,343.44, respectively. CONCLUSION: Approaches to care that lead to cost-effective utilization of health care resources should be pursued.

Burkitt lymphoma in pregnancy.

BACKGROUND: Burkitt lymphoma during pregnancy is a rare event, and outcomes have been poor. However, few patients were treated by current standards, with nearly half receiving single-agent cyclophosphamide or no chemotherapy. CASE: A patient with Burkitt lymphoma presenting at 11 6/7 weeks' gestation was treated with surgical resection of all visible disease and cytotoxic combination chemotherapy. The patient was disease free at 1 year after diagnosis. CONCLUSION: When Burkitt lymphoma is encountered in pregnancy, immediate cytotoxic combination chemotherapy is indicated.

Response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel and platinum-based combination regimens.

OBJECTIVE: The aim of this study was to evaluate the response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel-based chemotherapy. METHODS: A retrospective review of patients with recurrent ovarian cancer treated with surgical debulking and paclitaxel-based chemotherapy was performed. All cases received second-line treatment with a response evaluated by clinical or surgical means. Data analysis was conducted using the SAS statistical package. RESULTS: Fifty cases of advanced stage disease were available for review. Patients received paclitaxel and cisplatin or carboplatin with a 72.0% response rate. The median time to recurrence after primary treatment was 6 months. Second-line treatment included cisplatin or carboplatin (50%), Taxol (10%), or lutetium (22%), an intraperitoneal radiolabeled monoclonal antibody targeted to TAG-72. A 52.0% clinical response to salvage treatment was detected. With a median follow-up of 7 months, 68.0% of patients had experienced recurrence or progression of their disease. The median time to second recurrence was 5 months. Cases sensitive to initial paclitaxel-containing chemotherapy responded to any of the salvage treatments more frequently than chemotherapy-resistant tumors (88.5% versus 11.5%, P < 0.05). CONCLUSIONS: Recurrent ovarian cancer patients initially treated with paclitaxel-based chemotherapy frequently responded to salvage treatment. However, the duration of response was brief, and hospitalization for treatment-related side-effects was common. Tumor response to initial paclitaxel/platinum treatment was predictive of future response to second-line agents. Current salvage therapies appear to provide little benefit in cases of tumors resistant to primary chemotherapy.

A phase I study of paclitaxel, doxorubicin, and cisplatin in patients with previously untreated epithelial ovarian cancer.

OBJECTIVE: Although doxorubicin is not currently popular as a primary agent in ovarian cancer, overviews of previous studies suggest that the inclusion of doxorubicin may have improved outcome. The purpose of this phase I study was to determine the maximal dose of doxorubicin that could be added to standard doses of paclitaxel and cisplatin with G-CSF support. METHODS: Women with FIGO stage III or IV epithelial ovarian cancer were primarily treated with escalating doses of doxorubicin in combination with paclitaxel (135 mg/m2 over 24 h) and cisplatin (75 mg/m2) every 3 weeks. Doxorubicin was started at 30 mg/m2 and escalated by 10 mg/m2 per treatment level. All patients received G-CSF support. RESULTS: Eleven patients were treated at two dose levels. Dose limiting toxicity (DLT) was reached at the 40 mg/m2 dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DLT included renal toxicity and prolonged thrombocytopenia. Despite vigorous antiemetic regimens 60% of patients experienced severe nausea and vomiting. Nine patients were assessable for response. Eight patients have had a complete clinical response (89%). Of the five patients undergoing second-look laparotomy two were negative. CONCLUSIONS: The maximum tolerated dose of doxorubicin in this three-drug regimen is 30 mg/m2 with standard doses of paclitaxel and cisplatin. Hematologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea and vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated.

Histopathological variables predicting high-grade squamous intraepithelial lesions after large-loop excision of the transformation zone.

OBJECTIVE: Our aim was to determine whether histopathological variables predict persistent high-grade squamous intraepithelial lesions (HGSIL) after large-loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: All patients with cervical intraepithelial neoplasia (CIN) grade 2 or 3 on a LLETZ specimen with at least one follow-up Papanicolaou (Pap) test were identified. Histopathological variables were evaluated for the potential to predict HGSIL on a follow-up Pap test. Variables examined included endocervical margin status, ectocervical margin status, endocervical curettage (ECC) result, presence or absence of endocervical glandular involvement, and presence or absence of koilocytosis. RESULTS: Two hundred and nineteen cases were identified. A follow-up Pap test showed HGSIL in 16 patients (7.3%). Of the histopathological variables studied, only a positive ECC at the time of LLETZ conization predicted HGSIL on follow-up cytology (p =.0002). Endocervical margin status, ectocervical margin status, presence or absence of glandular involvement, and presence or absence of koilocytosis were not associated significantly with HGSIL at follow-up. CONCLUSION: Most histopathological factors from LLETZ conization do not predict reliably the presence of HGSIL at the time of follow-up Pap test. A positive ECC at the time of LLETZ, however, may predict those patients destined to have persistence or recurrence. These findings suggest that conservative follow-up is warranted after LLETZ conization.

Intraperitoneal radioimmunotherapy of ovarian cancer with 177Lu-CC49: a phase I/II study.

BACKGROUND: Twenty-seven ovarian cancer patients who failed chemotherapy entered a phase I/II trial of intraperitoneal 177Lu-CC49 antibody. METHODS: Patients had disease confined to the abdominal cavity +/- retroperitoneal lymph nodes, adequate organ function, and no previous radiation. RESULTS: The most common side effects were delayed, transient arthralgia (10/27) and marrow suppression with 1.665 GBq/m2 (45 mCi/m2), which was considered the maximum tolerated dose. One of thirteen patients with gross disease had >50% tumor reduction after therapy, whereas most others with gross disease progressed (one went off study with stable disease at 11 weeks). Seven of nine patients with <1-cm nodules progressed in < or =21 months, and two of nine remain without evidence of disease at 4 to 5 months. Of patients with microscopic or occult disease, one relapsed at 10 months and four of five remain without evidence of disease at >6 to 35 months. CONCLUSIONS: Marrow suppression was the dose-limiting toxic effect of intraperitoneal immunotherapy with 177Lu-CC49. Antitumor effects were noted against chemotherapy-resistant ovarian cancer, even at lower dose levels, and resulted in prolonged disease-free survival of most patients with microscopic disease. This form of treatment deserves further study.

Small-Cell Carcinoma of the Cervix Presenting with Severe Hypokalemia as a Manifestation of Cushing's Syndrome.

OBJECTIVES: A case of small-cell carcinoma of the cervix and severe hypokalemia is presented. The need for surveillance of paraneoplastic syndromes in these patients is emphasized. METHODS: The patient's clinical course is presented. The available literature regarding small-cell carcinoma of the cervix and Cushing's syndrome is reviewed. RESULTS: A 32-year-old woman had diagnosed small-cell carcinoma after simple hysterectomy. After radical parametrectomy, she developed liver metastases that did not respond to chemotherapy. Subsequently, she developed severe and unremitting hypokalemia, which was determined to be the initial manifestation of Cushing's syndrome secondary to ectopic adenocorticotropic hormone production. Typical clinical features of Cushing's syndrome were noted to arise during subsequent examinations. CONCLUSIONS: Though paraneoplastic syndromes associated with small-cell carcinoma of the cervix are rare, this case report describes one of these syndromes as an etiology for metabolic derangements.

Treatment of cervical dysplasia with large loop excision of the transformation zone: is endocervical curettage necessary?

Endocervical curettage (ECC) is done during most colposcopic examinations. To evaluate the need for routine ECC, we reviewed the records of all new patients seen in the colposcopy clinic at our institution from July 15, 1992, to April 15, 1993. During the study period, ECC was done in 341 patients with an adequate colposcopy. Only one case of mild dysplasia was discovered after ECC in the 123 patients referred for evaluation of cervical intraepithelial neoplasia (CIN) I or atypia seen on Pap smear. ECC specimens were positive for dysplastic cells in only 3 of 203 patients (1.4%) in whom biopsy revealed CIN I or atypia, and Pap smears for all 3 patients were suggestive of more severe lesions. Routine ECC during the initial colposcopic examination adds expense and may cause significant patient discomfort. ECC can be safely omitted in patients with CIN I on referral Pap smear and before large loop excision of the transformation zone for treatment of more severe lesions.

A decision analysis of practice patterns used in evaluating and treating abnormal Pap smears.

OBJECTIVE: The purpose of this study was to investigate contemporary methods of evaluating and treating abnormal Pap smears, in terms of their potential for excessive treatment and financial impact on health care delivery systems. METHODS: Clinical algorithms for the evaluation and treatment of abnormal Pap smears were constructed, taking into consideration different philosophies on the need for colposcopic biopsy, the role of cryotherapy, and LLETZ. The algorithms employed (1) colposcopy of all patients with cryotherapy of mild dysplasia and LLETZ of moderate to severe dysplasia; (2) colposcopy with observation of mild dysplasia, treatment of moderate dysplasia by cryotherapy, and severe dysplasia by LLETZ; (3) colposcopy of LGSIL Paps before treatment and immediate LLETZ of HGSIL; and (4) immediate LLETZ of LGSIL and HGSIL Paps. Each algorithm was theoretically applied to a cohort of colposcopy clinic patients based upon referral Pap smear, with excessive treatment and costs calculated. The cohort's repeat Pap smear, colposcopic biopsy, and candidacy for cryotherapy were included in the analysis. The decision to use repeat Pap smear in treatment planning, submit only diagnostic LLETZ pathology, and select immediate LLETZ candidates by HGSIL/severe dysplasia Pap smear was considered. Financial impact was calculated using nationwide fiftieth-percentile reimbursement costs for procedures and related pathology. RESULTS: Colposcopy provided little opportunity for excessive treatment. In contrast, 49.3% of cases subjected to immediate LLETZ would theoretically not have required treatment, if initially evaluated by colposcopy. The use of the subset of HGSIL cases encompassing severe dysplasia only identified patients suitable for immediate LLETZ, with an excessive treatment rate of only 2.8%. Traditional colposcopy (algorithm 2) would have been least expensive at $718 per patient. Algorithms 1 and 3 were intermediate at $785 and $754 per patient, respectively. Immediate LLETZ of all abnormal Paps (algorithm 4) would have been most costly at $838 per patient. CONCLUSIONS: The abandonment of colposcopy and reliance on immediate LLETZ for evaluation and treatment of cervical lesions would have been expensive and had significant potential for excessive treatment. Traditional colposcopic evaluation, coupled with observation of mild dysplasia, appeared to be the most cost-effective means of treating cervical dysplasia and had a low potential for excessive treatment.

Kinetic evidence for both a fast and a slow secretory pathway for apolipoprotein A-I in humans.

The kinetics of apolipoproteins A-I and A-II were examined in human subjects using leucine tracers administered intravenously. High density lipoproteins were separated and apoA-I and A-II were isolated. The specific activity or enrichment data for these apolipoprotein were analyzed by mathematical compartmental modeling. In 11 of 14 subjects studied with a bolus-injected [3H]leucine tracer, in 3 subjects studied similarly with [3H]leucine, and in one subject studied by primed dose, constant infusion of [3H]leucine, a rapidly turning-over apoA-I fraction was resolved. A similar component was observed in 7 of 10 studies of apoA-II. The apoA-I data were analyzed using a compartmental model (Zech, L.A. et al. 1983. J. Lipid Res. 24: 60-71) modified to incorporate plasma leucine as a precursor for apoprotein synthesis. The data permitted resolution of two apoA-I pools, one, C(2), turned-over with a residence time of less than 1 day, the other, C(1), a slowly turning-over pool, appeared in plasma after a delay of less than half a day. C(1) comprised the predominant mass of apoA-I and was also the primary determinant of the residence time of apoA-I. Although the mass of the fast pool, C(2), was considerably less than that of C(1), because of its rapid turnover, the quantities of apoA-I transported through this fast pathway were 2- to 4-fold greater. These kinetic studies indicate that apoA-I is secreted into both fast and slowly turning-over plasma pools. The latter is predominantly measured with radioiodinated apoA-I tracers. The data can be analyzed by postulating either separate input pathways to each of the pools or by assuming the fast pool is the precursor to the slow pool. Thus, apoA-I could be initially secreted as a family of particles that are rapidly cleared from plasma, and a portion of this apoprotein then reappears in a slowly turning-over pool that constitutes the major mass of apoA-I. The physiologic identity of these kinetically distinct apoA-I species is unknown; however, the fast pool of apoA-I demonstrated in these studies is strikingly similar to that seen in subjects with Tangier disease who lack the slow pool.