Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation.

BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy. METHODS: The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria. RESULTS: A cohort of 119 (61 previously untreated, 58 with relapsed disease) patients with AML (92 patients), advanced myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a further 10 patients. Five (36%) of 14 patients with VOD had received no prior antileukemic cytotoxic therapy, including 2 patients who received single-agent Mylotarg therapy. CONCLUSIONS: Mylotarg was shown to be associated with the development of potentially fatal VOD in patients with leukemia who had not received SCT. VOD occurred when Mylotarg was used either as a single agent or when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated patients who had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who receive Mylotarg therapy.

Effects of supplementation of organic and inorganic combinations of copper, cobalt, manganese, and zinc above nutrient requirement levels on postpartum two-year-old cows.

The objective of this study was to determine whether a combination of Cu, Co, Mn, and Zn in an organic or inorganic form fed at higher than nutrient recommendations for 2-yr-old cows from calving to breeding would affect pregnancy rate, calving date, calf performance, and cow liver and serum mineral concentrations. Crossbred 2-yr-old cows were used after calving in 1994 (n = 127) and 1995 (n = 109). Cows were blocked by calving date to one of three treatments: 1) no supplemental minerals (CTL), 2) organic minerals (ORG), or 3) inorganic minerals (ING). Minerals were fed for the same daily intake for both organic and inorganic treatments: Cu (125 mg), Co (25 mg), Mn (200 mg), and Zn (360 mg). Cows were individually fed a mineral-protein supplement with grass hay from calving (February-March) to before breeding (May 15). Hay intakes were calculated using chromium oxide boluses to determine fecal output. Fecal excretion of minerals was calculated following trace element analysis of feces. Liver biopsies were obtained before calving, after calving (start of supplementation), at the end of supplementation, and in midsummer. Over 2 yr, more cows did not become pregnant (P < .01) in ORG (11/78) and ING (11/78) treatments than in CTL (0/80) treatments. A treatment x year interaction was found for day of conception. Cows in the ORG group conceived later (P < .01) than cows in the ING or CTL groups in 1994. In 1995, there was no difference (P > .10) in day of conception among groups. Liver Zn and Mn concentrations were not different (P > .10) and Cu concentrations increased (P < .01) for the ORG and ING groups. Cows in the ORG and ING groups had higher (P < .01) concentrations of Cu, Mn, and Zn in the feces than the CTL cows. Trace elements in the feces did not differ for ORG and ING groups. Results indicate that combinations of Cu, Co, Mn, and Zn fed at higher levels than are required reduced reproductive performance.

Effects of sire, dam traits, calf traits, and environment on dystocia and subsequent reproduction of two-year-old heifers.

A study was conducted over 3 yr to evaluate effects of sire birth weight EPD, calf birth weight and shape, and heifer pelvic area and weight, individually and in combination, on dystocia and subsequent rebreeding of 2-yr-old heifers. Heifers (n = 550), MARC II yearlings, were assigned for breeding to one of four Angus sires with birth weight EPD of -.95, -82, +2.9, and +2.7 kg. At calving, heifers were assisted as needed. A gauge attached to the cal puller recorded applied traction pressure. Analysis of traction pressure detected only slightly larger amounts of variation (2 to 3%) affecting dystocia than the standard five-point scoring system. Dam weight did not affect calving difficulty score (CDS), except dam birth weights were heavier (P < .05) for CDS 5 (Caesarean section) than CDS 1 (unassisted). Dams requiring Caesarean section had smaller pelvic areas (P < .05), with no other differences among CDS. The CDS increased as calf birth weight and cal external measurements increased. Low EPD sires produced calves with smaller (P < .05) birth weights and smaller calf head and food circumferences and caused less dystocia than high EPD sires. The CDS did not affect subsequent pregnancy rates but did affect conception date of the second calf. Calves delivered by Caesarean section were lighter (P < .05) at weaning than other calves but had similar slaughter weights. As mean winter temperature increased (6.1 degrees C) from yr 1 to 3, calf birth weight decreased (4.6 kg) and calving difficulty decreased 23%. Results indicate sire birth weight EPD, calf birth weight and shape, dam pelvic area, and climate affected CDS, and CDS affected subsequent conception date.

Results of the Galileo probe nephelometer experiment.

The nephelometer experiment carried on the Galileo probe was designed to measure the jovian cloud structure and its microphysical characteristics from entry down to atmospheric pressure levels greater than 10 bars. Before this mission there was no direct evidence for the existence of the clouds below the uppermost cloud layer, and only theoretical models derived from remote sensing observations were available for describing such clouds. Only one significant cloud structure with a base at about 1.55 bars was found along the probe descent trajectory below an ambient pressure of about 0.4 bar, although many indications of small densities of particle concentrations were noted during much of the descent.

Effects of Synovex C implants on growth rate, pelvic area, reproduction, and calving performance of replacement heifers.

Two trials were conducted to evaluate effects of Synovex C implants on replacement heifers, given at two different ages. Crossbred heifer calves (n = 370) were allotted to four treatments: 1) nonimplanted controls, 2) implanted at 2 mo, 3) implanted at 6 mo, and 4) implanted at both 2 and 6 mo of age. Heifers implanted at 2 mo gained 7 kg more (P = .01) by 6 mo than those not implanted at 2 mo. No differences were found in 22-mo weights. All implanted heifers had larger (P = .01) yearling pelvic area than controls. All heifers implanted at 6 mo continued to have larger (P = .01) pelvic area at 22 mo. All implanted heifers had higher (P = .05) occurrence of non-ovulatory estrus. No differences were found among treatments in percentage of heifers puberal before breeding, in estrus first 21 d of breeding, or in first-service conception rate. In only one trial, pregnancy first 21 d and total pregnancy in 63-d breeding season were decreased (P = .05) by implanting at 6 mo. At subsequent calving, an interaction existed between the effects of the 2- and the 6-mo implant for calf birth weight and pelvic area:birth weight ratio. A single implant at either 2 or 6 mo decreased (P = .01) calving difficulty score; and implanting at both 2 and 6 mo showed the greatest reduction in calving difficulty. Implants had no significant long-term effects on reproduction or calf production of 2-yr-old cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I/II trial of recombinant gamma-interferon in patients with renal cell carcinoma: immunologic and biologic effects.

Thirteen patients with metastatic renal cell carcinoma were entered on a Phase I/II trial of recombinant gamma-interferon (gamma-IFN). Patients (3) were entered on escalating dose levels, and each patient was escalated to the next dose until an individual maximum tolerated treatment dose (MTD) was established. Multiple parameters of biologic response were measured. Patients were studied twice baseline and at frequent intervals after the initial treatment and every treatment until the patient's individual MTD was reached. The MTD for most patients was less than 75 X 10(6) U/m2. Small, but statistically significant, enhancement of monocyte antibody-dependent cellular cytotoxicity and mononuclear cell inhibition of MBL-2 growth were noted in vitro at gamma-IFN concentrations greater than 250 U/ml. Clinically obvious biologic effects were observed: fever, chills, hypotension, and malaise. However, laboratory assays of peripheral blood mononuclear cell natural killer cell activity, tumor (MBL-2) growth inhibition, antibody-dependent cellular cytotoxicity, lymphoblastic T-cell subsets, and 2'5'-oligonucleotide synthetase were not altered in vivo.

Unsuccessful in vitro fertilization: a follow-up study.

Results from a follow-up questionnaire completed by 28 women who had unsuccessfully completed one or more trials of in vitro fertilization (IVF) are reported. The mean time lapse since completing IVF was 8.4 months. During that period, 33% of the respondents had applied for adoption and 11% had secured an adoptive child. More than half the respondents had abandoned biological attempts to conceive and 52% felt as though they had "resolved" the infertility crisis. Nevertheless, 93% of the respondents indicated that they would participate in any new reproductive options that would enhance the likelihood of a biological pregnancy! The results and implications of this study are discussed.

Sexual expression and its determinants in the post-menopausal woman.

Anatomic, hormonal, psychosocial and psychosexual variables of sexual expression were evaluated in 69 non-patient post-menopausal women. Subjects received a 2-h individually administered interview, a gynecologic examination with subjective scoring of vaginal atrophy, and serum determinations of estrone, estradiol, and androstenedione, testosterone, FSH and LH. Sexual repertoire of the 34 coitally active (coitus greater than 3 X monthly) was compared to the 29 coitally inactive (coitus less than 10 X yearly) subjects. The majority of subjects engaged in traditional sexual activities, with emphasis on physical affection and coitus. The active and inactive women were similar on all demographic variables except family income and weight/height ratio. The inactive women were slightly more obese and had lower incomes. Post-menopausal patterns of sexual activity correlated with post-menopausal sexual expression as did partner availability and function. The active women had a significantly higher LH level. No correlation was found between current or ideal sexual frequency and androgen or estrogen levels.

Vaginal atrophy in the postmenopausal woman. The importance of sexual activity and hormones.

The effect of sexual activity on vaginal atrophy was investigated in a group of 52 postmenopausal women (mean age, 57 years). Subjects were divided into two groups: sexually active (intercourse frequency, three or more times monthly) and sexually inactive (intercourse frequency, less than ten times yearly). Two gynecologists examined all subjects and completed an index of vaginal atrophy that assessed six genital dimensions. Blood samples were also analyzed by radioimmunoassay for levels of circulating estrone, estradiol, androstenedione, testosterone, follicle-stimulating hormone, and luteinizing hormone (LH). As predicted, less vaginal atrophy was apparent in the sexually active women as opposed to the sexually inactive women. Further, women with less vaginal atrophy had significantly higher mean levels of androgens (androstenedione and testosterone) and gonadotropins (particularly LH). We discuss herein the implications of this study, particularly the importance of androgens in reducing atrophy and maintaining sexual interest.

Saturn's Magnetic Field and Magnetosphere.

The Pioneer Saturn vector helium magnetometer has detected a bow shock and magnetopause at Saturn and has provided an accurate characterization of the planetary field. The equatorial surface field is 0.20 gauss, a factor of 3 to 5 times smaller than anticipated on the basis of attempted scalings from Earth and Jupiter. The tilt angle between the magnetic dipole axis and Saturn's rotation axis is < 1 degrees , a surprisingly small value. Spherical harmonic analysis of the measurements shows that the ratio of quadrupole to dipole moments is < 10 percent, indicating that the field is more uniform than those of the Earth or Jupiter and consistent with Saturn having a relatively small core. The field in the outer magnetosphere shows systematic departures from the dipole field, principally a compression of the field near noon and an equatorial orientation associated with a current sheet near dawn. A hydromagnetic wake resulting from the interaction of Titan with the rotating magnetosphere appears to have been observed.

Multicolor observations of phobos with the viking lander cameras: evidence for a carbonaceous chondritic composition.

The reflectivity of Phobos has been determined in the spectral region from 0.4 to 1.1 micrometers from images taken with a Viking lander camera. The reflectivity curve is flat in this spectral interval and the geometric albedo equals 0.05 +/- 0.01. These results, together with Phobos's reflectivity spectrum in the ultraviolet, are compared with laboratory spectra of carbonaceous chondrites and basalts. The spectra of carbonaceous chondrites are consistent with the observations, whereas the basalt spectra are not. These findings raise the possibility that Phobos may be a captured object rather than a natural satellite of Mars.

Jupiter's Magnetic Field. Magnetosphere, and Interaction with the Solar Wind: Pioneer 11.

The Pioneer 11 vector helium magnetometer provided precise, contititious measurements of the magnetic fields in interplanetary space, inside Jupiter's magnetosphere, and in the near vicinity of Jupiter. As with the Pioneer 10 data, evidence was seen of the dynanmic interaction of Jupiter with the solar wind which leads to a variety of phenomena (bow shock, upstream waves, nonlinear magnetosheath impulses) and to changes in the dimension of the dayside magnetosphere by as much as a factor of 2. The magnetosphere clearly appears to be blunt, not disk-shaped, with a well-defined outer boundary. In the outer magnetosphere, the magnetic field is irregular but exhibits a persistent southward component indicative of a closed magnetosphere. The data contain the first clear evidence in the dayside magnetosphere of the current sheet, apparently associated with centrifugal forces, that was a donminatnt feature of the outbound Pionieer 10 data. A modest westward spiraling of the field was again evident inbound but not outbound at higher latitudes and nearer the Sun-Jupiter direction. Measurements near periapsis, which were nearer the planet and provide better latitude and longitude coverage than Pioneer 10, have revealed a 5 percent discrepancy with the Pioneer 10 offset dipole mnodel (D(2)). A revised offset dipole (6-parameter fit) is presented as well as the results of a spherical harmonic analysis (23 parameters) consisting of an interior dipole, quadrupole, and octopole and an external dipole and quadrupole. The dipole moment and the composite field appear moderately larger than inferred from Pioneer 10. Maximum surface fields of 14 and 11 gauss in the northern and southern hemispheres are inferred. Jupiter's planetary field is found to be slightly more irregular than that of Earth.

Polarized magnetic field fluctuations at the apollo 15 site: possible regional influence on lunar induction.

High-frequency (5 to 40 millihertz) induced lunar magnetic fields, observed at the Apollo 15 site near the southeastern boundary of Mare Imbrium and the southwestern boundary of Mare Serenitatis, show a strong tendency toward linear polarization in a direction radial to the Imbrium basin and circumferential to the Serenitatis basin, a property that could be indicative of a possible regional influence on the induction.

Magnetic field of jupiter and its interaction with the solar wind.

Jupiter's magnetic field and its interaction with the magnetized solar wind were observed with the Pioneer 10 vector helium magnetometer. The magnetic dipole is directed opposite to that of the earth with a moment of 4.0 gauss R(J)(3) (R(J), Jupiter radius), and an inclination of 15 degrees lying in a system III meridian of 230 degrees . The dipole is offset about 0.1 R(J) north of the equatorial plane and about 0.2 R(J) toward longitude 170 degrees . There is severe stretching of the planetary field parallel to the equator throughout the outer magnetosphere, accompanied by a systematic departure from meridian planes. The field configuration implies substantial plasma effects inside the magnetosphere, such as thermal pressure, centrifugal forces, and differential rotation. As at the earth, the outer boundary is thin, nor diffuse, and there is a detached bow shock.

Whole body response of the moon to electromagnetic induction by the solar wind.

A comparison has been made of the interplanetary magnetic field as measured both by Apollo 12 on the lunar surface and by Explorer 35 in orbit around the moon. Two examples are given, one of a step change in the field vector and another of a sinusoidally varying field. A large response measured on the surface is attributed to confinement of the induced field lines between the streaming solar plasma and the high-conductivity interior. A steep bulk electrical conductivity gradient in the lunar crust is implied, with a confining layer roughly 100 kilometers deep.

Earth's Bow Shock: Elapsed-Time Observations by Two Closely Spaced Satellites.

Coordinated observations of the earth's bow shock were made as Vela 3A and Explorer 33 passed within 6 earth radii of each other. Elapsed time measurements of shock motion give directly determined velocities in the range 1 to 10 kilometers per second and establish the existence of two regions, one of large amplitude magnetic "shock" oscillations and another of smaller, sunward, upstream oscillations. Each region is as thick as 1 earth radius, or more.