Search PubMed⌕ Search

Biomedical subjects

Y Tanaka

Publications and source records attributed to Y Tanaka.

At least 235 records · Page 13Linked to original sources

Effect of linear alkylbenzene sulfonate on population growth of Daphnia galeata: a life table evaluation.

The chronic effect of linear alkylbenzene sulfonate (LAS12) on a daphnid species (Daphnia galeata) was examined by the life table experiment. The estimated responses in the intrinsic rate of population growth r were analyzed with two alternate concentration-response functions, i.e., the power function and the quadratic function. Based on the best-fit power function model with biases corrected by the jackknife procedure, the population-level EC50, which is defined as the concentration of chemicals that reduces the population growth rate (the intrinsic rate of natural increase) by 50%, was estimated as 2.5 mg/L. The 48-h acute immobility test yielded EC50 of 4.6 mg/L. The population-level effect of LAS12 on this test species is considerably more sensitive than the acute lethal effects to neonates.

Age Factors↗

Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice.

Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2(d)) or syngeneic DC from C57BL/6 mice (syn-DC, H-2(b)). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Allo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2(d)/H-2(b))and MUC1 antigen. By contrast, only H-2(b) and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.

Animals↗

Applicability of a mobile accelerator for intraoperative radiation therapy to colorectal cancer.

PURPOSE: Intraoperative radiation therapy is reportedly effective for local control and pain relief in colorectal cancer. However, this treatment requires a large number of medical personnel, which hinders expanded use of this method. A mobile electron linear accelerator for intraoperative radiation therapy has been developed and is now commercially available. This report analyzes the applicability of this accelerator to colorectal cancer. The applicability of the mobile accelerator is analyzed based on its specifications by simulating the intraoperative radiation therapy delivered to these patients with a conventional intraoperative radiation therapy unit. METHODS: From 1987 to 1999, 49 colorectal cancer patients underwent 54 surgical resections and received intraoperative radiation therapy to 75 sites. RESULTS: The mean intraoperative radiation therapy dose for colorectal cancer with the conventional unit was 22 (range, 10-30) Gy. The mean electron energy level was 10 (range, 3-30) MEV. Applicator size ranged from 4 to 10 cm in diameter. The mobile accelerator can achieve a dose rate of 10 Gy/min and an applicator unit size range of 3 to 10 cm in diameter, facilitating intraoperative radiation therapy for colorectal cancer. The electron energy limitation (12 MEV at maximum) suggests that the indications for this machine are limited. In our experience, 30 percent of patients received intraoperative radiation therapy with electron energy levels exceeding 12 MEV. Of these cases, 81 percent had macroscopic residual tumor and 69 percent had pain. CONCLUSION: An intraoperative radiation therapy mobile accelerator can cover 72 percent of the irradiation sites covered using our conventional unit. This accelerator is useful for intraoperative radiation therapy with curative intent for patients with no or slight residual tumor. Patients with gross residual tumor and pain may not be suitable.

Adult↗

Bilateral transient radial nerve palsies in an infant after cardiac surgery.

PURPOSE: To describe the case of an infant who suffered bilateral transient radial nerve palsies after cardiac surgery. CLINICAL FEATURES: A one-month-old baby was found to have bilateral wrist and finger drop after the removal of splints that has been applied to the right hand for 14 days and to the right hand for six days during perioperative management of Blalock-Taussig shunt surgery. The hand splints had been applied to the forearms with adhesive silky tape to keep peripheral vascular lines in place. The patient also suffered from several episodes of cardiogenic shock, hypoxemia and generalized edema relating to cardiac dysfunction during this fine period. Given the findings of no impairment of median or ulnar nerves and brachioradial muscle, it was suspected that bandaging with adhesive tapes caused peripheral radial nerve damage at the level of posterior interosseus nerve on forearm. Diminished oxygen delivery and edema may additionally have contributed to peripheral nerve ischemia. The aforementioned neurologic symptoms resolved spontaneously after several days. CONCLUSION: Prolonged compression by bandaging of splints on forearm may have resulted in ischemic damage to the posterior interosseus nerve branch combined with extensor carpi radialis longus nerve branch of the radial nerve. We should attempt to reduce the frequency and duration of splinting of the extremities, especially in sedated, paralyzed babies, given the potential risk of compression neuropathy.

Arteriovenous Shunt, Surgical↗

Validation of the functional fitness age (FFA) index in older Japanese women.

Functional fitness age (FFA), which we previously described, is a measure of functional age that reflects a person's overall physical ability to complete daily tasks such as preparing meals and performing various household chores. The purpose of this study was to validate FFA in two elderly populations: 1) older subjects from different communities, and 2) older subjects participating in an exercise intervention program. FFA was calculated from 4 performance tests: performing arm curls; moving beans with chopsticks; demonstrating functional reach; and sitting and walking around two cones. The first study group was selected from 4 different communities (N=127), and was subdivided into a less active group (N=87) and an active group (N=40). The results of the 4 tests for the less active group were not significantly different from those for the original validation group used in developing the FFA equation. The FFA of the less active group (71.1+/-7.7 yrs) was not different from their chronological age (70.4+/-6.6 yrs). In the active group, except for the arm curls, test scores were significantly higher than those of the original validation group. The FFA of the active group (66.2+/-5.1 yrs) was significantly younger than their chronological age (70.9+/-4.2 yrs). Another group of 14 older women (79.5+/-3.9 yrs) was recruited for pre- and post-training testing. After the 3-month exercise program, they showed significant improvements in sitting and walking around two cones and functional reach; their FFA decreased significantly from 81.5+/-5.0 yrs to 78.3+/-4.5 yrs. The control group selected from the same community (N=16, 79.8+/-5.3 yrs) showed no significant changes in the 4 performance tests, and their FFA remained unchanged. These results indicate that our FFA is highly cross-validated for different Japanese communities, and is sensitive to changes associated with participation in an exercise intervention program.

Activities of Daily Living↗

Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions.

Gangliosides GD3, GD2 and GM2, which are the major gangliosides expressed on most human cancers of neuroectodermal and epithelial origin, have been focused on as effective targets for passive immunotherapy with monoclonal antibodies. We previously developed a chimeric anti-GD3 mAb, KM871, and a humanized anti-GM2 mAb, KM8969, which specifically bound to the respective antigen with high affinity and showed potent immune effector functions. Humanization of anti-ganglioside antibody is expected to enhance its use for human cancer therapy. In the present study, we generated a chimeric anti-GD2 mAb, KM1138, and further developed the humanized form of anti-GD2 and anti-GD3 mAbs by the complementarity-determining regions grafting method. The resultant humanized anti-GD2 mAb, KM8138, and anti-GD3 mAb, KM8871, showed binding affinity and specificity similar to those of their chimeric counterparts. In addition, both humanized mAbs had functional potency comparable to the chimeric mAbs in mediating the immune effector functions, consisting of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The production of these humanized anti-ganglioside mAbs, with potent effector functions and low immunogenicity, precedes the evaluation of the therapeutic value of anti-ganglioside mAbs in passive immunotherapy and the target validation for ganglioside-based vaccine therapy.

Amino Acid Sequence↗

Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification.

BACKGROUND: The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. METHODS: Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. RESULTS: According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). CONCLUSIONS: These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL.

Female↗

HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.

The vasorelaxant profile of a novel azulene-1-carboxamidine derivative, HNS-32 [N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine, CAS 186086-10-2], was investigated in the isolated rabbit aorta precontracted with high KCl, noradrenaline (NA) or phorbol 12, 13-dibutyrate (PDBu) and compared with those of nifedipine and nitroglycerin. In preparations without endothelium, HNS-32 elicited concentration-dependent, full inhibition of contractions elicited by high KCI (80 mM), NA (3x10(-6) M) or PDBu (10(-6) M). In contrast, nifedipine inhibited only the contraction elicited by membrane depolarization with high KCl. Nitroglycerin also attenuated high-KCl-, NA- and PDBu-elicited contractions effectively, although full suppression was obtained only for NA-elicited contraction. Whilst the relaxant effect of HNS-32 was not affected by the presence of endothelium, the relaxant response to acetylcholine was endothelium dependent. Addition of excess Ca2+ restored both the HNS-32-reduced tension in muscle precontracted with high KCI and the nifedipine-mediated tension decrease. Relaxation elicited by HNS-32 was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2'-furyl)adenine (SQ 22,536, 10(-4) M), the soluble guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10(-5) M) or a cocktail of K+ channel blockers (glybenclamide 10(-6) M, tetraethylammonium 2x10(-3) M, apamin 10(-7) M, 4-aminopyridine 10(-4) M and Ba2+ 10(-5) M). These findings indicate that HNS-32 inhibits both L-type Ca2+ channel-dependent and -independent vascular contraction. Blockade of Ca2+ entry through L-type Ca2+ channels may be involved in the inhibitory effect of HNS-32 on the contraction due to membrane depolarization with high KCl. On the other hand, HNS-32 seems to inhibit Ca2+ channel-independent contraction via mechanism(s) other than elevation of cyclic nucleotides (cAMP and cGMP) and opening of K+ channels.

Animals↗

Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium.

The possible involvement of the endocardial endothelium in the positive inotropic response of the mouse left atrium to acetylcholine was examined pharmacologically. In mouse left atria, acetylcholine produced a biphasic inotropic response: a transient decrease in contractile force followed by a late increase. The positive response was not affected by the presence of phentolamine and propranolol, but was almost abolished by pretreatment of the preparation with 1% Triton X-100, which denudes the endocardium of its endothelium. Nordihydroguaiaretic acid, NG-nitro-L-arginine, BQ-123 and BQ-788 had no effect on the inotropic responses to acetylcholine, but indomethacin completely abolished the positive response. Prostaglandins and their analogues had a positive inotropic effect with a potency order PGF2alpha>PGD2>PGE2>U46619, whereas beraprost had no effect. Neither Triton X-100 pretreatment nor the presence of indomethacin affected the positive inotropic effect of PGF2alpha. Acetylcholine and PGF2alpha prolonged the action potential duration similarly. These results suggest that the acetylcholine-induced positive inotropic response in mouse left atria is mediated by prostaglandin released from the endocardial endothelium.

Acetylcholine↗

MaxiK channel-mediated relaxation of guinea-pig aorta following stimulation of IP receptor with beraprost via cyclic AMP-dependent and -independent mechanisms.

The present study was aimed to elucidate the cellular pathway(s) controlling vascular relaxation triggered by stimulation of prostaglandin I2 (PGI2, IP) receptor with a stable PGI2 analog, beraprost. Beraprost caused a concentration-dependent relaxation in de-endothelialized guinea-pig aorta contracted with prostaglandin F2alpha (PGF2alpha). Beraprost-induced relaxation was almost abolished in high-KCl-contracted tissue, indicating a major role of K+ conductances. In contrast to other PGI2 analogs (e.g. cicaprost and iloprost), beraprost-induced relaxation was practically abolished by a selective voltage and Ca2+-activated K+ (MaxiK, BK) channel blocker Iberiotoxin (10(-7) M) or by tetraethylammonium (2 x 10(-3) M). The relaxation induced by beraprost was not significantly affected by other K+ channel blockers glibenclamide (10(-6) M) or Ba2+ (10(-5) M), but was slightly attenuated by 4-aminopyridine (10(-4) M). Beraprost increased intracellular cyclic AMP levels, suggesting a role for cyclic AMP-dependent pathways. A selective inhibitor of cyclic AMP-specific phosphodiesterase, RO-20-1724 (10(-4) M), significantly potentiated beraprost-induced relaxation. Iberiotoxin (10(-7) M) completely counteracted this potentiation. Moreover, tension decrement due to forskolin (3 x 10(-7) M) or 8-bromo-cyclic AMP (10(-2) M) was thoroughly restored by Iberiotoxin (10(-7) M), confirming a role for a cyclic AMP-dependent mechanism. However, SQ 22,536 (10(-4) M), an adenylyl cyclase inhibitor, did not affect beraprost-induced relaxation though it almost totally inhibited the elevation of cyclic AMP contents induced by beraprost, suggesting the existence of an additional mechanism that is cyclic AMP-independent. Moreover, cholera toxin (CTX, 1 microg/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), significantly suppressed PGF2alpha-induced contraction both in the absence and presence of SQ 22,536 (10(-4) M). Iberiotoxin (10(-7) M) was also capable of restoring the relaxation induced by CTX. These findings suggest that MaxiK channel plays a primary role in mediating smooth muscle relaxation following stimulation of IP receptor with beraprost in guinea-pig aorta. Both cyclic AMP-dependent and -independent pathways contribute to the MaxiK channel-mediated relaxation following IP receptor stimulation in this vascular tissue. Direct regulation of MaxiK channels by Gs may partly account for the cyclic AMP-independent relaxant mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗

Antidepressant-like effects of aniracetam in aged rats and its mode of action.

RATIONALE: Aniracetam has been reported to be efficacious for treating poststroke depression, but no studies that basically examined the antidepressive effects have been made. OBJECTIVE: We aimed to test the antidepressant-like property of aniracetam in rats and to clarify the mechanisms of action through the interaction studies with some receptor antagonists. METHODS: Antidepressant-like effects of aniracetam and various classes of compounds including different antidepressants were examined in a forced swim test with young (9 weeks old) and aged (25-30 months old) rats. Rats were exposed to a 5-min swim in a test session on day 2 following a 15-min swim in a training session on day 1, and immobility time during the period on day 2 was measured. The test compounds were administered subacutely (three doses over 2 days) or acutely (0.5 h before the testing). RESULTS: Standard antidepressants except for tandospirone significantly reduced immobility time in both young and aged rats. Aniracetam (10-100 mg/kg PO) failed to decrease immobility time in young rats, but it (100 mg/kg PO) significantly shortened immobility in aged rats, the effects of which were mainly mimicked by combined treatment of the metabolites, 2-pyrrolidinone and N-anisoyl-GABA. The effects of aniracetam was reversed completely by mecamylamine (10 mg/kg IP) or haloperidol (0.1 mg/kg IP) and slightly by ketanserin (1 m/kg IP) but was potentiated by scopolamine (0.03 mg/kg IP). CONCLUSIONS: These results indicate that aniracetam acts more effective when the forced swim stress-induced immobility is accompanied with brain dysfunction that occurs with aging. The antidepressant-like activity of aniracetam, which is probably due to the combined effects of 2-pyrrolidinone and N-anisoyl-GABA, may be mediated by mainly facilitating dopaminergic transmission (dopamine release and dopamine D2 receptor activation) through nicotinic acetylcholine receptor stimulation.

Administration, Oral↗

Trabecular domain factor and its influence on the strength of cancellous bone of the vertebral body.

The effects of architectural differences on the strength of cancellous bone of the vertebral body have not been clarified. This study was aimed at determining the influence of trabecular domain factor (TDF), a new histomorphometric parameter, on the maximum compressive strength (MCS) in vertebral cancellous bone. TDF is a variation coefficient representing the ratio dispersion of the area of each trabecula (Sd) to the area of its domain (D). A Voronoi diagram was used to determine trabecular domains. The materials comprised 35 lumbar vertebral bodies obtained at autopsy from 35 subjects aged 25-83 years. A mechanical test sample (12 x 12 x 16 mm) was cut out from each right half, and two large, undecalcified, horizontal sections from each left half. The fields (144 mm2 x 2) for image analyses were symmetrical with those for mechanical test samples in the other half of the same vertebral body. Bone volume (BV/TV), Sd, and D were semiautomatically measured. BV/TV correlated negatively with TDF (r = -0.73). Multiple regression analysis revealed the contributions of BV/TV (partial r = 0.75, p < 0.001) and TDF (partial r = -0.42, p < 0.02) to MCS. The model with BV/TV and TDF predicted MCS, 1.50 +0.15 BV/TV -0.03 TDF, more accurately (R2 = 0.83) than that with BV/TV alone (r2 = 0.79). We conclude that the bone volume primarily contributes to the MCS of vertebral cancellous bones but that the influence of TDF on the fragility becomes increasingly important as the bone volume decreases.

Adult↗

Microbial desulfurization of alkylated dibenzothiophene and alkylated benzothiophene by recombinant Rhodococcus sp. strain T09.

The dibenzothiophene (DBT) desulfurizing operon, dsz, was introduced into various benzothiophene (BT)-desulfurizing bacteria using a Rhodococcus-E. coli shuttle vector. Of the tested recombinant bacteria, only those from Rhodococcus sp. strain T09 grew with both DBT and BT as the sole sulfur source. These recombinant cells desulfurized not only alkylated BTs, but also various alkylated DBTs, producing alkylated hydroxybiphenyls as the desulfurized products. Recombinant strain T09 also desulfurized alkylated DBT in an oil-water, two-phase resting-cell reaction. The dsz operon had the same desulfurizing activity when inserted into the vector in either orientation, indicating that the promoter region of the operon was functional in strain T09.

Alkylation↗

Gamma/delta T cells provide innate immunity against renal cell carcinoma.

Host immune function plays a certain role against the development of renal cell carcinomas (RCCs), but the mechanism is not entirely understood. Human gamma/delta (gamma/delta) T cells defend the body against infection. In this study, we clarify the role of gamma/delta T cells in the surveillance system against RCCs by analyzing the gamma/delta T cells in peripheral blood mononucleocytes (PBMs) and tumor infiltrating lymphocytes (TILs) from 41 patients with RCCs. The results showed that the number of gamma/delta T cells expressing V gamma 2 and V delta 2 in variable elements of TCR was elevated in the PBMs in 10 patients, but not in any of 32 healthy individuals. The proportion of patients with an elevated number of gamma/delta T cells (> 10%) increased with cancer stage. The level of the gamma/delta T cells decreased after surgery. The gamma/delta T cells in the TILs were more activated than those in the PBMs. Evaluation of the junctional diversity of TCR V gamma 2 and V delta 2 chains showed that the increased peripheral blood gamma/delta T cells were oligoclonal rather than polyclonal. Taken together, our findings suggest that gamma/delta T cells recognize certain RCC-related antigens and play a role in the surveillance system against RCCs.

Adult↗

Optimum treatment strategy for superficial esophageal cancer: endoscopic mucosal resection versus radical esophagectomy.

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

Aged↗

The platelet-sparing effect of paclitaxel is not related to changes in the pharmacokinetics of carboplatin.

PURPOSE: To determine whether the platelet-sparing effect of paclitaxel is related to changes in pharmacology of carboplatin. METHODS: A group of 32 patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.) carboplatin-based chemotherapy with carboplatin alone or in combination with cyclophosphamide or paclitaxel, and the relationship between the pharmacology of serum platinum and thrombocytopenia was examined. The target AUC of i.p. carboplatin was 6.5 mg min/ml. Cyclophosphamide was administered intravenously at 400 mg/m2 after i.p. carboplatin and paclitaxel at 175 mg/m2 was given before i.p. carboplatin. RESULTS: Ten patients received i.p. carboplatin alone, 10 received cyclophosphamide and 12 received paclitaxel. The ages of the patients, body surface area, serum creatinine, platelet count before chemotherapy, and the total dose of carboplatin in each patient were similar in all groups. The measured AUC, Cmax, T 1/2, and MRT were similar in these groups. The nadir platelet counts were significantly higher (P = 0.0018) in patients treated with i.p. carboplatin with paclitaxel (12.1 +/- 4.3 x 10(4)/mm3) compared with carboplatin alone (5.2 +/- 3.3 x 10(4)/mm3) or with cyclophosphamide (5.2 +/- 4.8 x 10(4)/mm3). The percentage decrease in platelet counts was significantly lower (62.5 +/- 18.2%) in patients treated with paclitaxel than in the other two groups (81.5 +/- 12.6% carboplatin alone, 88.7 +/- 7.9% with cyclophosphamide). CONCLUSION: The addition of paclitaxel or cyclophosphamide to i.p. carboplatin did not alter the pharmacology of serum platinum. Thrombocytopenia was significantly less in patients treated with carboplatin in combination with paclitaxel. The platelet-sparing effect of paclitaxel is not related to changes in the pharmacology of carboplatin.

Age Factors↗