PubMed Health⌕ Search

Biomedical subjects

J Rinehart

Publications and source records attributed to J Rinehart.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH). DESIGN: Phase III, multicenter, open-label randomized trial. SETTING: In vitro fertilization (IVF) centers in North America. PATIENT(S): Healthy female partners (n = 313) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated. INTERVENTION(S): Patients were randomized to receive one COH cycle with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection. OUTCOME MEASURE(S): Number of oocytes retrieved, pregnancy rates, endocrine variables, and safety variables. RESULT(S): The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62.4% and 61.9% in the ganirelix and leuprolide groups, respectively, and implantation rates were 21.1% and 26.1%. Clinical and ongoing pregnancy rates per attempt were 35.4% and 30.8% in the ganirelix group and 38.4% and 36.4% in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11.9% and 0.6%) than with leuprolide (24.4% and 1.1%). CONCLUSION(S): Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.

Adult↗
PubMed2001

Genomics and the evolution of aminoacyl-tRNA synthesis.

Translation is the process by which ribosomes direct protein synthesis using the genetic information contained in messenger RNA (mRNA). Transfer RNAs (tRNAs) are charged with an amino acid and brought to the ribosome, where they are paired with the corresponding trinucleotide codon in mRNA. The amino acid is attached to the nascent polypeptide and the ribosome moves on to the next codon. Thus, the sequential pairing of codons in mRNA with tRNA anticodons determines the order of amino acids in a protein. It is therefore imperative for accurate translation that tRNAs are only coupled to amino acids corresponding to the RNA anticodon. This is mostly, but not exclusively, achieved by the direct attachment of the appropriate amino acid to the 3'-end of the corresponding tRNA by the aminoacyl-tRNA synthetases. To ensure the accurate translation of genetic information, the aminoacyl-tRNA synthetases must display an extremely high level of substrate specificity. Despite this highly conserved function, recent studies arising from the analysis of whole genomes have shown a significant degree of evolutionary diversity in aminoacyl-tRNA synthesis. For example, non-canonical routes have been identified for the synthesis of Asn-tRNA, Cys-tRNA, Gln-tRNA and Lys-tRNA. Characterization of non-canonical aminoacyl-tRNA synthesis has revealed an unexpected level of evolutionary divergence and has also provided new insights into the possible precursors of contemporary aminoacyl-tRNA synthetases.

Amino Acyl-tRNA Synthetases↗
PubMed1999

Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility.

OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.

Adult↗
PubMed1999

Impact of the "physician factor" on pregnancy rates in a large assisted reproductive technology program: do too many cooks spoil the broth?

OBJECTIVE: To determine whether in one program with unified treatment protocols, patients can expect varying treatment outcomes with different physicians. DESIGN: Retrospective data analysis. SETTING: University-affiliated infertility center with 14 physicians. PATIENT(S): One thousand eight hundred fifty IVF cycles performed consecutively between August 1995 and June 1997. INTERVENTION(S): The pregnancy rate and implantation rate per ET were evaluated for individual physicians between August 1995 and June 1996 (phase I). Physicians with lower success rates underwent strict supervision from July 1996 to June 1997 (phase II). MAIN OUTCOME MEASURE(S): Variations in success rates between physicians. RESULT(S): The pregnancy rate varied among the physicians from 13.2%-37.4%, and the implantation rate varied from 4.4%-14%. Some physicians' outcomes improved between phase I and phase II of the study, whereas others' did not. The pregnancy and implantation rates varied significantly for some physicians, depending on whether they were responsible for the choice of stimulation protocol, supervision of cycle monitoring, or ET in their own or other physicians' patients. CONCLUSION(S): Outcomes of IVF vary depending on the treating physician. Lower than expected pregnancy and implantation rates usually are not caused by poor ET techniques alone, but appear to be disproportionately the consequences of poor cycle stimulation.

Embryo Implantation↗
PubMed1997

Lysis of intrauterine adhesions using gynecoradiologic techniques.

OBJECTIVE: To present further experience with in-office lysis of intrauterine adhesions under fluoroscopic control using a specially designed catheter. DESIGN: Prospective study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Seventeen infertile patients undergoing routine gynecoradiologic investigation as part of an initial infertility workup. INTERVENTION(S): The initial hysterosalpinography was performed with a commercially available uterine catheter that seals off the uterine cavity before injection of contrast. If intrauterine adhesions were diagnosed, an immediate attempt at lysis was made using the catheter's balloon tip or hysteroscopic scissors, which were inserted through the main port of the catheter. The procedures were carried out using a paracervical block or IV analgesia. MAIN OUTCOME MEASURE(S): Normal uterine cavity after lysis of intrauterine adhesions. RESULT(S): Seventeen patients underwent lysis of intrauterine adhesions. In 13 patients (9 mild, 3 moderate, and 1 severe), the adhesions were lysed successfully (81.2%). Among those, nine procedures were performed with the balloon and four with scissors. In 4 cases (2 moderate and 2 severe), lysis of adhesions was only partially successful. These procedures had to be abandoned prematurely because of patient discomfort before attempting the use of scissors (n = 1), extravasation of dye into the myometrium making visualization difficult (n = 1), and thick, fibrotic adhesions that were resistant to scissors (n = 2). CONCLUSION(S): In-office lysis of intrauterine adhesions under gynecoradiologic control can be carried out safely in the majority of patients, using minimally invasive techniques. The potential cost savings in comparison with endoscopic procedures, which require utilization of expensive operating room time, are especially relevant in today's cost-conscious managed care environment. Only failures of in-office procedures would reach the operating room under the algorithm proposed here.

Catheterization↗
PubMed1997

Limited success using the "flare" protocol in poor responders in cycles with low basal follicle-stimulating hormone levels during in vitro fertilization.

OBJECTIVE: To assess an alternate protocol for stimulating poor responders. DESIGN: Prospective clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Eighty poor responders. INTERVENTION(S): Stimulation was withheld until patients fulfilled the following criteria: basal FSH < or = 12 mIU/mL (conversion factor to SI unit, 1.00) with concurrent E2 level < or = 100 pg/mL (conversion factor to SI unit, 3.671), and P level < or = 1.0 ng/mL (conversion factor to SI unit, 3.467). They then started leuprolide acetate on cycle day 2 and a high dose of gonadotropins on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation response and pregnancy rates (PRs). RESULT(S): Nineteen cycles (23.8%) were canceled because of poor ovarian response. The mean E2 level on day of hCG was 2,578 +/- 1,339 pg/mL (9,464 +/- 4,915 pmol/L) (range, 789 to 5934 pg/mL [2,896 to 21,784 pmol/L]). The number of oocytes retrieved was 10 +/- 6.6 (range, 1 to 37). Nine patients did not have ET (failed fertilization [n = 5], no cleavage of preembryos [n = 3], freeze all [n = 1]). The number of pre-embryos transferred was 3.9 +/- 1.6 (range, 1 to 8). The clinical pregnancy rate was 7 of 61 (11.5%) per retrieval, and 7 of 52 (13.4%) per transfer with an implantation rate of 7 of 201 (3.5%). Three patients miscarried with an ongoing PR of 4 of 61 (6.5%) per retrieval and 4 of 52 (7.6%) per transfer. CONCLUSION(S): Poor responders undergoing controlled ovarian hyperstimulation with the "flare" protocol in cycles with low basal FSH will often show adequate ovarian response and reach oocyte retrieval and ET. The PRs, however, remain low.

Adult↗
PubMed1997

Locally advanced head and neck cancer: combined chemotherapy and radical radiation therapy for organ and function preservation (interim report).

PURPOSE: This phase II study was performed to assess the feasibility of organ preservation after combined chemotherapy and radical radiation therapy in patients with resectable, locally advanced head and neck cancer. MATERIALS AND METHODS: Twenty-four patients had surgically resectable stage III (n = 9) and stage IV (n = 15) squamous cell carcinoma of the head and neck. Initially, they received two to three courses of neoadjuvant chemotherapy (5-fluorouracil and cisplatin). Patients in whom response was seen were then treated definitively with two courses of cisplatin chemotherapy administered concomitantly with radical radiation therapy. Patients in whom no response was seen underwent salvage surgery or other standard therapy. RESULTS: The response rate after induction chemotherapy was 84% (including 42% complete remission). Complete remission after concomitant chemotherapy and radical radiation therapy was 83%. After a median follow-up of 18 months (maximum, 3.5 years), 18 patients (75%) remained recurrence free. Grade 3 or 4 treatment-related toxicity was experienced, but there was no treatment-related mortality. CONCLUSION: Combined chemotherapy and radical radiation therapy used in this study resulted in organ and function preservation in the majority of patients with resectable stage III and IV head and neck cancer.

Adult↗
PubMed1997

Phase 1 trial of recombinant human interleukin-1 beta (rhIL-1 beta), carboplatin, and etoposide in patients with solid cancers: Southwest Oncology, Group Study 8940.

Recombinant human interleukin-1 beta (rhIL-1 beta) was evaluated in a phase 1 clinical trial in which patients with metastatic or unresectable solid tumors received carboplatin and etoposide in cycle 1 and carboplatin, etoposide, and rhIL-1 beta in cycle 2. Recombinant hIL-1 beta was given intravenously for 5 days in one of three schedules: (1) immediately postchemotherapy, (2) delayed for 5 days after chemotherapy, or (3) concurrently with chemotherapy. Four dose levels of rhIL-1 beta were evaluated: 20, 50, 100, and 200 ng/kg. The doses of carboplatin and etoposide were not changed between cycle 1 and cycle 2 so that the effect of rhIL-1 beta on chemotherapy-induced hemato-toxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluable for rhIL-1 beta toxicity and for the effect of rhIL-1 beta on hematotoxicity of carboplatin and etoposide. The major toxicities of rhIL-1 beta were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1 beta was not determined since the toxicities at all dose levels were similar. However, only 3/8 patients at the 200 ng/kg level received all 5 IL-1 beta infusions. We compared the effect of rhIL-1 beta on hematotoxicity of carboplatin/etoposide by comparing peripheral blood count parameters between cycles 1 and 2: rhIL-1 beta given postchemotherapy significantly increased absolute neutrophil count (AND) nadirs and improved neutrophil recovery times regardless of rhIL-1 beta dose level. Platelet count parameters were also improved when rhIL-1 beta was given postchemotherapy although these changes did not reach statistical significance. Thus, IL-1 beta exhibited extensive hematological effects but the usefulness of this agent in clinical practice will be limited by extensive toxicity at all tested dose levels.

Adult↗
PubMed1997

Corticosteroids alter hematopoiesis in vitro by enhancing human monocyte secretion of granulocyte colony-stimulating factor.

The mechanism of corticosteroid alteration of hematopoiesis is not completely elucidated. Employing an endotoxin free system, we examined the mechanisms by which hydrocortisone succinate (HCS) enhanced human bone marrow (BM) colony forming unit granulocyte-macrophage (CFU-GM) proliferation. Interleukin-1beta (IL-1) (1 ng/mL), granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 ng/mL), or the combination, induced minimal CFU-GM proliferation unless HCS was added to the cultures (10-25 vs. 80-125 colonies/4x10(5) BM mononuclear cells). Supernatants produced by incubating mononuclear cells with IL-1 + GM-CSF +/- HCS were examined for their capacity to induce CFU-GM proliferation: IL-1 and/or GM-CSF failed to induce supernatants capable of supporting CFU-GM proliferation unless HCS was present. Analysis of the cytokines produced by mononuclear cell subpopulations demonstrated that HCS markedly enhanced IL-1-induced monocyte secretion of granulocyte (G)-CSF. Furthermore, the minimal effective concentration of IL-1 required to induce G-CSF release was reduced 10-fold (from 1 to 0.1 ng/mL) and the G-CSF released was increased 5-fold at an IL-1 concentration of 1 ng/mL. In contrast, IL-1-induced monocyte secretion of tumor necrosis factor (TNF) was inhibited by HCS. HCS enhanced G-CSF secretion at physiologic concentrations (10 microg/dL), whereas progesterone had no effect. HCS alone had no effect on G-CSF secretion or mRNA expression while IL-1+HCS resulted in a 3-fold increase in G-CSF mRNA levels. These data suggest for the first time that corticosteroids increase secretion of an essential component of the lymphohematopoietic cytokine-growth factor system.

Adrenal Cortex Hormones↗
PubMed1995

Corticosteroid alteration of carboplatin-induced hematopoietic toxicity in a murine model.

Corticosteroids exhibit extensive hematopoietic effects both in vitro and in vivo. Some of the previously studied effects suggested that corticosteroids may alter hematopoietic toxicity of chemotherapeutic agents. In this study, we examined (1) the optimum dose and schedule of cortisone acetate (CA) to reduce hematopoietic toxicity of carboplatin (CB) and (2) possible mechanisms involved in this protective effect. CA given subcutaneously at 0.5 mg/d per mouse for 7 days before CB reduced CB-induced mortality due to neutropenia from 88% in controls to 14% in CA-treated mice (P < .05). Lower CA doses were not effective. Three days of pretreatment (but not 1 day) was as effective as 7 days. CA given after CB had no effect on mortality. Pharmacokinetic studies of CA at 0.5 mg per mouse demonstrated blood levels of cortisol achievable in patients (peak level, 82 micrograms/dL). CA treatment markedly reduced spleen cell number and colony-forming units-granulocyte/macrophage (CFU-GM) as well as bone marrow CFU-GM. Bone marrow CFU-GM removed from CA-treated mice demonstrated increased resistance to platinum and increased resistance to high specific activity 3H-thymidine. These findings suggest that treatment of mice with CA induces cellular resistance of hematopoietic precursors to platinum and, thus, reduces CB hematotoxicity. CA or other corticosteroids may be useful in reducing clinical toxicity of CB.

Animals↗
PubMed1995

The paternal inheritance of the centrosome, the cell's microtubule-organizing center, in humans, and the implications for infertility.

Successful fertilization in humans, achieved when parental chromosomes intermix at first mitosis, requires centrosome restoration and microtubule-mediated motility. Imaging of inseminated human oocytes reveals that the sperm introduces the centrosome. The centrosome then nucleates the new microtubule assembly to form the sperm aster--a step essential for successful fertilization. Oocytes from some infertile patients failed to complete fertilization because of defects in uniting the sperm and egg nuclei, indicating that failure to properly effect the cytoplasmic motions uniting the nuclei results in human infertility. These discoveries have important implications for infertility diagnosis and managing reproduction.

Centrosome↗
PubMed1995

Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study.

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.

Adult↗
PubMed1994

Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system.

Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activities, eg, fever, nausea, malaise, and hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female, 6 weeks) were treated for 7 days subcutaneously with cortisone acetate (CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2 micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell counts, splenic granulocyte-macrophage colony-forming units, and spleen cell number, and protected mice from lethal doses of carboplatin (200 mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the day after completion of the 7 days of IL-1 administration. CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL-1 administered to mice at 8 micrograms/d/mouse for 5 days induced decreased activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5 to 2 micrograms/d) was not toxic. CA in a dose-dependent manner blocked all of the above mentioned toxicities when administered 24 hours and 30 minutes before each IL-1 injection. CA also decreased IL-1-induced increase in plasma tumor necrosis factor levels at the time point examined.

Animals↗
PubMed1994

Multiple cycles of dose-intensive cyclophosphamide, etoposide, and cisplatinum (DICEP) produce durable responses in refractory non-Hodgkin's lymphoma.

Patients whose lymphoma is resistant to standard treatment regimens continue to do poorly, with only an occasional patient achieving long-term remission even with bone marrow transplantation. Twenty-three patients with primarily refractory (11), or refractory relapsed (12) non-Hodgkin's lymphoma were treated with repeated cycles of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) without bone marrow transplantation. Each cycle of DICEP consisted of cyclophosphamide (2500 mg/m2/day, days 1-2), etoposide (500 mg/m2/day, days 1-3), and cisplatin (50 mg/m2/day, days 1-3). Twelve patients (52%) have achieved a complete response and 6 (26%)r a partial response. Three of the complete responders remain continuously free of disease for 19, 29, and 32 months, and 3 more are disease-free at 58, 59, and 65 months after receiving further therapy. Three-year survival for all patients is 45%. Patients with a good initial performance status (Zubrod 0 or 1) had a 58% complete response rate and a 2-year survival rate of 53%. One of 19 patients with an initial performance status of 0 or 1 had treatment-related mortality. Repeated cycles of DICEP can produce long-term responses in patients with refractory non-Hodgkin's lymphoma.

Adult↗
PubMed1991

Interleukin-2 therapy enhances salicylate oxidation by blood granulocytes.

These studies determined the effect of interleukin-2 (IL-2) immunotherapy on the oxidative metabolism of the blood granulocytes of eight patients with metastatic renal cancer. We quantitated the rate of the hexose monophosphate shunt activity (HMPS), hydrogen peroxide (H2O2) production, and salicylate oxidation of the unstimulated and phorbol myristate acetate (PMA)-stimulated granulocyte cultures before, during, and after a 5-day continuous infusion of IL-2. There was no change in the rate of HMPS activity. However, the rate of salicylate oxidation of the unstimulated and PMA-stimulated cultures of these patients was significantly increased after the therapy was complete. Overall, there was no increase in the rate of H2O2 production, although the PMA-stimulated cultures of three of eight patients had a twofold higher production of H2O2 after treatment compared with the pretreatment values. The enhanced rate of salicylate oxidation by the granulocytes after treatment indicates that these cells were "stimulated" in vivo to produce a potent oxidant, which is most likely hydroxyl radical or an oxidant of comparable activity. Further, the granulocytes were primed ("activated"), since they had an augmented response to PMA. IL-2 did not stimulate the oxidative metabolism of granulocyte cultures in vitro, suggesting that the IL-2 effect in vivo is not a direct one. Our results indicate that IL-2 immunotherapy is associated with the activation of blood granulocyte oxidative metabolism and that these activated granulocytes may be related to some of the toxic side effects of IL-2 therapy such as the capillary leak syndrome. Further oxidant injury to the granulocytes may explain the reported defect in chemotaxis.

Carcinoma, Renal Cell↗
PubMed1990

Long-term care pharmacy services: a new dimension of pharmacy practice.

Pharmacists providing care to patients must have a commitment to quality patient care, have well-developed operations systems, possess refined clinical skills, and be able to effect excellent communication with the clinical and administrative staff. These attributes of pharmacy practice should exist in both the acute care and long-term care settings. Pharmacy practice in the long-term care setting, a unique position due to the everchanging definition of long-term care, may best be referred to as an alternative site for the application of contemporary pharmacy distribution and clinical systems for patient care over an extended period.

Drug Therapy↗
PubMed1989

Expansion of lymphokine-activated killer cells for clinical use utilizing a novel culture device.

Two major problems encountered in the application of lymphokine-activated killer (LAK) cell therapy in man are the massive culture volumes required for LAK cell induction and the paucity of LAK cells available for administration (human doses are less than or equal to 10% of effective murine LAK cell doses). We have, therefore, developed and tested a plastic porous culture device, Sclair plastic bags (E.I. DuPont De Nemours Co.), that can be utilized at virtually any volume and does not require rotation for optimal use. Normal or patient lymphocytes were cultured in the device or in plastic 16 mm wells at 1-20 X 10(6)/ml RPMI 10% human sera with 1500 pM interleukin-2 for 4 days: LAK cell activity did not decline despite high cell densities. The device was equal to the 16 mm wells in induction of normal donor and patient LAK cell activity when either autologous fresh tumor or Raji targets were used. In a non-therapeutic clinical evaluation we isolated and stored in liquid nitrogen autologous tumor cells from 11 patients with cancer. 2-6 weeks post-operatively lymphocytes and mononuclear cells from these patients and paired normal donors were obtained and LAK cells were induced in Sclair bags or standard culture wells. Autologous patient LAK cell activity and normal donor LAK cell activity against patient's tumor cells were equivalent in the Sclair culture device and culture well system. Lymphocyte recovery and [3H]thymidine incorporation were also similar. Subsequently, we developed an expansion scheme utilizing the device in which cell density was maintained at optimal levels by changing media and reducing cell concentration after 6, 10 and 14 days of culture. We were able to expand LAK cell number 5-10-fold with no loss of LAK cell activity in this time frame utilizing both normal and patient cells. In this system plasma and sera were equivalent in their capacity to support LAK cell expansion but less than 10% plasma or sera supported suboptimal activation. Thus, we have developed a practical system to augment the number of LAK cells available for human LAK cell therapy and simultaneously reduce the complexity and volume of the induction system.

Animals↗