The Nature of the Long-Lived Excited State in a NiII Phthalocyanine Complex Investigated by X-Ray Transient Absorption Spectroscopy.

The nature of the photoexcited state of octabutoxy nickel(II) phthalocyanine (NiPcOBu8 ) with a 500 ps lifetime was investigated by X-ray transient absorption (XTA) spectroscopy. Previous optical, vibrational, and computational studies have suggested that this photoexcited state has a ligand-to-metal charge transfer (LMCT) nature. By using XTA, which provides unambiguous information on the local electronic and nuclear configuration around the Ni center, the nature of the excited state of NiPcOBu8 was reassessed. Using X-ray probe pulses from a synchrotron source, the ground- and excited-state X-ray absorption spectra of NiPcOBu8 were measured. Based on the results, we identified that the excited state exhibits spectral features that are characteristic of a Ni1, 3 (3dz2 ,3dx2-y2 ) state rather than a LMCT state with a transiently reduced Ni center. This state resembles the (d,d) state of nickel(II) tetramesitylphorphyrin. The XTA features are rationalized based on the inherent cavity sizes of the macrocycles. These results may provide useful guidance for the design of photocatalysts in the future.

Optical properties of shaped silver nanoparticles.

The influence of shape and dielectric property of surrounding media on surface plasmon absorption band of silver nanoparticles was studied. Spherical silver nanoparticles (d = 5.6 nm) synthesized in water using NaBH4 as a reducing agent are transferred in non-polar solvent (chloroform) with phase-transfer reagent oleylamine. The absorption spectrum of oleylamine-capped silver nanoparticles dispersed in chloroform shows a strong surface plasmon resonance band that is 19 nm red-shifted compared to unmodified particles in water. The values for peak position and corresponding half widths are compared with theoretical calculations based on Mie theory. Prismatic and plate-like silver nanoparticles were synthesized in water using trisodium citrate as a reducing agent and cetyltrimethylammonium bromide as stabilizer. Due to structural anisotropy of prismatic and plate-like silver nanoparticles three surface plasmon resonance bands were observed in absorption spectrum. Nanocomposites consisting of non-spherical silver nanoparticles and polyvinyl alcohol exhibit different optical properties compared to water colloid. Instead of three surface plasmon bands, nanocomposite film has only one peak at 460 nm. Reason for appearance of single surface plasmon resonance band in nanocomposite film was discussed according to Maxwell-Garnet theory.

Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.

Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC).

The failure of convenional chemotherapy in relapsed or refractory and other poor risk AML patients has been linked to expression of the multidrug resistance gene (mdr 1) product P-glycoprotein (P-gp). PSC 833 is a non-competitive inhibitor of P-gp and has been shown in vitro and in vivo to restore sensitivity of resistant tumor cells to anticancer drugs (ACDs). Induction chemotherapy consisting of cytarabine (C) in combination with PSC 833 and escalating doses of mitoxantrone (M) and etoposide (E) over 5 or 6 days were tested in two phase I/II studies in poor prognosis AML. Overall, 59 patients were evaluated: their age ranged between 18 and 70 years. Fourteen patients had primary refractory disease, 25 had relapsed within 9 months from first complete remission (CR), 5 were in second relapse, 10 had secondary AML, and 4 had relapsed post-bone marrow transplantation. PSC 833 was given as a constant i.v. infusion at a rate of 10 mg/kg/24 h for 5 or 6 days, depending on the duration of chemotherapy. In both studies a loading dose of 2 mg/kg of PSC 833 was given on day 1. In the 5-day regimen, the final study doses of the cytotoxic agents were C 1 g/m2/d, M 4.0 mg/m2/d, and E 40 mg/m2/d. In the 6-day regimen, the final study doses of the cytotoxic agents were C 1 g/m2/d, M 4.5 mg/m2/d and E 30 mg/m2/d. The combined efficacy results of both studies indicate that PSC-MEC is active in all treatment indications, complete remission being achieved in 2/5 (40%) second relapses, 8/25 (32%) early relapses, 3/10 (30%) secondary AML, 3/15 (20%) refractory patients and 1/4 (25%) post-BMT relapses. Based on historical controls, this observed overall CR rate (29%) is higher than expected in this high risk patient population. Our data indicate that, in refractory/relapsed AML patients, PSC-MEC regimens had encouraging antileukemic effects, is well tolerated, and has led to Phase III trials in this setting.

Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar).

A potential mechanism of chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from refractory or relapsed AML. In a multicenter phase II clinical trial, 37 patients with these poor risk forms of AML were treated with PSC 833 (Valspodar; Novartis Pharmaceutical Corporation, East Hanover, NJ), a potent inhibitor of the MDR-1 efflux pump, plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Pharmacokinetic (PK) interactions of etoposide and mitoxantrone with PSC were anticipated, measured in comparison with historical controls without PSC, and showed a 57% decrease in etoposide clearance (P =.001) and a 1.8-fold longer beta half-life for mitoxantrone in plasma (P <.05). The doses of mitoxantrone and etoposide were substantially reduced to compensate for these interactions and clinical toxicity and in Cohort II were well tolerated at dose levels of 4 mg/m2 mitoxantrone, 40 mg/m2 etoposide, and 1 g/m2 C daily for 5 days. Overall, postchemotherapy marrow hypoplasia was achieved in 33 patients. Twelve patients (32%) achieved complete remission, four achieved partial remission, and 21 failed therapy. The PK observations correlated with enhanced toxicity. The probability of an infectious early death was 36% (4 of 11) in patients with high PK parameters for either drug versus 5% (1 of 20) in those with lower PK parameters (P =.04). P-gp function was assessed in 19 patients using rhodamine-123 efflux and its inhibition by PSC. The median percentage of blasts expressing P-gp was increased (49%) for leukemic cells with PSC-inhibitable rhodamine efflux compared with 17% in cases lacking PSC-inhibitable efflux (P =.004). PSC-MEC was relatively well tolerated in these patients with poor-risk AML, and had encouraging antileukemic effects. The Eastern Cooperative Oncology Group is currently testing this regimen versus standard MEC chemotherapy in a phase III trial, E2995, in a similar patient population.

c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets.

We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the gene cad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad and gadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes.

The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.

The c-Myc and E2F transcription factors are among the most potent regulators of cell cycle progression in higher eukaryotes. This report describes the isolation of a novel, highly conserved 434 kDa protein, designated TRRAP, which interacts specifically with the c-Myc N terminus and has homology to the ATM/PI3-kinase family. TRRAP also interacts specifically with the E2F-1 transactivation domain. Expression of transdominant mutants of the TRRAP protein or antisense RNA blocks c-Myc- and E1A-mediated oncogenic transformation. These data suggest that TRRAP is an essential cofactor for both the c-Myc and E1A/E2F oncogenic transcription factor pathways.

Comparison of synthetic serum substitute and fetal cord serum as media supplements for in vitro fertilization: a prospective, randomized study.

OBJECTIVE: To compare the value of synthetic serum substitute and fetal cord serum (FCS) as protein supplements in the media used for IVF. DESIGN: Prospective, randomized study of 45 patients undergoing IVF. SETTING: Private infertility practice. INTERVENTION(S): The protein supplement for use in IVF medium was randomized prospectively to synthetic serum substitute or FCS. MAIN OUTCOME MEASURE(S): Oocyte fertilization rate, incidence of embryo arrest, number of embryos transferred, ongoing pregnancy rate, and implantation rate were assessed. RESULT(S): There was no significant difference in the fertilization rate, incidence of embryo arrest, number of embryos transferred, ongoing pregnancy rate, and implantation rate. CONCLUSION(S): Synthetic serum substitute is a better alternative to FCS as a protein supplement for IVF because of its availability and cost effectiveness. Synthetic serum substitute can be used in culture medium for sperm washing, insemination, culture, and transfer translating to decreased technician time without a significant difference in fertilization, pregnancy, or implantation rate.

The effect of positive semen bacterial and Ureaplasma cultures on in-vitro fertilization success.

A total of 342 couples planning to undergo in-vitro fertilization (IVF) were examined for the presence of bacteria in semen prior to and during the procedure. Pregnancy rates were analysed retrospectively to ascertain any adverse affects if > 10000 colony forming units (CFU)/ml bacteria were detected in the semen sample. The most common bacteria isolated from semen were Enterococcus spp. (73%). The presence of these bacteria did not affect the pregnancy rate of the patients with positive cultures prior to (32%) or during (37%) the IVF procedure compared with those patients in whom no bacteria were detected (32%). Those patients with semen cultures positive for Escherichia coli prior to the IVF procedure, but which cleared after treatment had a higher pregnancy rate (60%) compared with those patients who were positive for E.coli at the time of the attempt. The group of patients with Staphylococcus aureus in the semen at the time of IVF also demonstrated a low pregnancy rate (17%). Of the patients. 36 (11%) had positive Ureaplasma cultures from the screening test carried out on the semen and 22% became pregnant after successful treatment. None of the three patients with persistently positive cultures became pregnant. In conclusion, the presence of Enterococcus in semen does not affect pregnancy rates following IVF. E.coli, S.aureus and Ureaplasma urealyticum may have a negative effect and should be treated.

Laparoscopically assisted gamete intrafallopian transfer with local anesthesia and intravenous sedation.

OBJECTIVE: To determine the length of procedure, length of recovery, patient tolerance, complications, and pregnancy rate (PR) of laparoscopically assisted GIFT performed during local anesthesia with i.v. sedation. DESIGN: A retrospective study. SETTING: Freestanding private ambulatory surgical center. PATIENTS: Thirty-one consecutive couples with infertility. INTERVENTIONS: Laparoscopically assisted GIFT during local anesthesia with i.v. sedation. MAIN OUTCOME MEASURES: Surgery time, recovery time, patient tolerance, PR, miscarriage rate, and complications. RESULTS: Cannulation of at least one fallopian tube was achieved successfully in all patients. The average surgery time was 64 +/- 12 minutes (mean +/- SD). The average recovery time was 92 +/- 30 minutes. The PR was 39% with an ongoing PR of 32%. There were no intraoperative or postoperative complications. CONCLUSION: Local anesthesia with IV sedation for GIFT using a two-puncture laparoscopic technique was well tolerated by the patients. Our ongoing PR of 32% compares very favorably with other series using general anesthesia.

Use of the flare-up protocol with high dose human follicle stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders.

OBJECTIVE: To analyze the effect of high dose human FSH in combination with hMG with a flare-up leuprolide acetate (LA) protocol in patients undergoing IVF at risk for a poor response. DESIGN: Prospective. SETTING: Free-standing ambulatory IVF center. PATIENTS: Two hundred eighty-four patients underwent a LA screening test for IVF. Patients with a lack of flare response were considered at risk for a poor response and underwent ovarian stimulation with the flare-up LA protocol in combination with high dose human FSH and hMG. RESULTS: The poor responder group was compared with the good responders on the flare-up LA protocol and to patients undergoing ovulation induction with a luteal phase LA protocol. There were 53 poor responder flare-up LA cycles, 177 good responder flare-up LA cycles, and 54 luteal phase LA cycles. The cancellation rate was higher in poor flare-up LA responders (11.3 percent) compared with good flare-up LA responders (1.1 percent) and luteal phase LA cycles (1.8 percent). Peak E2 levels, number of oocytes, and number of embryos were significantly higher in the good flare-up LA responders. Fertilization rate was similar in all groups. Ongoing pregnancy rate per retrieval was 28 percent in good responders, 29 percent in poor responders, and 33 percent in luteal phase LA patients. Only one patient (0.4 percent) was hospitalized for severe ovarian hyperstimulation. CONCLUSION: The flare-up protocol with high-dose human FSH and hMG is a very good alternative for patients who are at high risk for a poor response. Although peak E2 and number of oocytes were significantly lower in this group, the patients who responded had the same fertilization and pregnancy rate as the good responders. Cancellation rate remains high in poor responders.

A Mono-Percoll separation technique improves sperm recovery of normal and male factor specimens when compared with the swim-up technique.

The purpose of this study was to determine the effects of a simplified 80% Mono-Percoll sperm separation procedure on both normal and male factor semen samples compared with the standard swim-up technique. The parameters examined include sperm concentration, motility and morphology, total motile functional spermatozoa and percentage recovery. Normal patients demonstrated enhanced sperm parameters with the Mono-Percoll compared with the swim-up technique for concentration (67 x 10(6) versus 42 x 10(6)/ml, P < 0.001), motility (66 versus 59%, P < 0.001), morphology (56 versus 49%, P < 0.005) and percentage recovery (60 versus 42%, P < 0.005). Male factor patients showed enhanced sperm parameters with the Mono-Percoll procedure compared with the swim-up technique for motility (53 versus 42%, P < 0.05) and percentage recovery (54 versus 29%, P < 0.005), with no significant difference in concentration and morphology. In summary, the Mono-Percoll sperm recovery procedure is significantly better than the swim-up technique for male factor patients and patients with normal sperm parameters.

Differences between early and late onset of substance abuse: an inpatient experience.

Of 100 consecutive patients admitted to an inpatient alcohol and drug abuse ward, approximately four fifths reported the onset of substance use before 18 years of age. The majority used both alcohol and drugs, and had a history of problems with school authorities and suicidal ideation. We found general and sex-specific patterns of substance use among both depressed and nondepressed substance users and abusers.

Self-referent processing of age-specific material.

College students and elderly subjects made self- and other-descriptiveness judgments about trait adjectives that were age-specific descriptors. The young adults favored endorsement of traits that had been judged descriptive of young adults, compared to traits that had been judged descriptive of elderly adults. However, elderly adults endorsed an equivalent number of young and elderly traits. This indicates that content specificity with regard to age is more a characteristic of young adults than elderly people, with elderly adults being "schematic" for descriptors of both young and older people. Nonetheless, for the elderly subjects, the speed of self-reference decisions was slower for the young traits relative to the elderly traits, as if the young traits were somewhat less accessible. Although elderly adults recalled fewer adjectives overall than young adults, their pattern of recall was similar for self- versus other-referenced items. Thus, it seem unlikely that age differences in spontaneous self-referencing account for the general age deficit in retention.

Diagnostic laparoscopy under local anesthesia for evaluation of infertility.

Diagnostic laparoscopy is routinely performed in outpatient departments. At Stanford University's Gyn/Ob Department Clinic, this procedure is performed with the client's active cooperation by using local anesthesia. In addition to the significant benefit of decreased risk of surgical anesthesia, outpatient surgery is more convenient and more economical for the client and the facility. The laparoscopic procedure is described in detail. The facilities, nursing responsibilities, surgeon's qualifications, and criteria for patient selection are included.

Regional hyperthermia for cancer.

The clinical use of regional hyperthermia combined with radiation therapy, chemotherapy, or both in 107 patients with advanced cancer is reported. Surgery was subsequently carried out in eight patients. The radiofrequency equipment used is capable of heating tumors at any depth with few adverse side effects. Complete responses to therapy occurred in 16 percent of patients, and partial responses in 52 percent. Striking pain relief was observed in both responders and nonresponders.