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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 253 records · Page 14Linked to original sources

Detection of premature luteinization with serum progesterone levels at the time of the postcoital test.

Poor cervical mucus (CM) may be caused by a number of factors, including premature luteinization, local cervical effects, and inadequate folliculogenesis. In an attempt to distinguish between these causes of poor CM, we obtained progesterone (P) levels at the time of postcoital tests (PCTs) in infertile women during spontaneous or clomiphene citrate (CC)-stimulated cycles. The amount of CM, viscosity, ferning, spinnbarkeit, and cellularity were each scored from 0 to 3 points on the day after detection of the urinary luteinizing hormone surge (luteal day 1). The charts of 46 such patients were retrospectively reviewed. Eleven control patients with good CM scores (greater than 10) had low P levels (less than 2.5 ng/mL). Of the remaining 35 cycles, 19 were marked by low P levels, and 16 were accompanied by P levels of greater than 2.5 ng/mL. Overall, 94.4% of CC-stimulated cycles versus 64.3% of spontaneous cycles had abnormal CM scores (less than 9). On the basis of these inappropriately elevated P levels, premature luteinization can be cited as the cause of poor mucus quality. In fact, premature luteinization may be responsible for some of the purported antiestrogenic effects of CC. Therefore, it is appropriate to draw a P level at the time of a poor PCT, particularly in cycles stimulated by CC.

Cervix Mucus↗

Gonadotropin-releasing hormone agonist improves the efficiency of controlled ovarian hyperstimulation/intrauterine insemination.

OBJECTIVE: Leuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles. DESIGN: During an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized. SETTING: Referral center at a tertiary care hospital. PATIENTS: One hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II. MAIN OUTCOME MEASURES: Pregnancy/IUI is compared between the two groups. RESULTS: Group II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births. CONCLUSIONS: In our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage.

Female↗

The luteal phase during gonadotropin therapy: effects of two human chorionic gonadotropin regimens.

OBJECTIVE: Luteal phase abnormalities are known to complicate ovulation induction with gonadotropins. This study was performed to test the effect of a modified human chorionic gonadotropin (hCG) regimen on the luteal phase during gonadotropin treatment. DESIGN: Fifteen women from a private practice setting volunteered to be studied during each of two nonconception, gonadotropin-stimulated cycles. After ovarian stimulation with human menopausal gonadotropins (hMG), hCG was administered either as a single dose of 10,000 IU (single dose) or in two divided doses of 5,000 IU given 1 week apart (split dose). MAIN OUTCOME MEASURES: Early, midluteal, and late luteal estradiol (E2) and progesterone (P) levels and luteal phase lengths were measured, and their median values and intraquartile ranges (IQR) compared using nonparametric analysis. RESULTS: Early and midluteal E2 and P levels were similar regardless of which hCG regimen was administered. The median late luteal E2 level was 1,146.0 pg/mL (the IQR ranged from 633 to 1,650, IQR = 1,017) with the split-dose regimen and 240.0 pg/mL (the IQR ranged from 150 to 460, IQR = 310) with the single-dose regimen. The median late luteal P level was 108.0 ng/mL (the IQR ranged from 58.5 to 129, IQR = 70.5) with the split-dose regimen and 4.2 ng/mL (the IQR ranged from 1.9 to 11.7, IQR = 9.8) with the single-dose regimen. Median luteal phase lengths were 16 days (the IQR ranged from 15 to 17, IQR = 2) for the split-dose regimen and 11 days (the IQR ranged from 10 to 12, IQR = 2) for the single-dose regimen. CONCLUSION: In hMG-stimulated cycles, a second dose of hCG given during the midluteal phase significantly increases late luteal E2 and P levels and consistently lengthens the luteal phase.

Adult↗

The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia.

Mice homozygous for a mutant allele (an/an) causing a lifelong macrocytic anemia (Hertwig's anemia) also demonstrate an inability to deliver their offspring, despite normal ovulation, conception, implantation, and fetal development. We investigated the roles of estrogen and relaxin in the etiology of the reproductive defect in the Hertwig's anemia mice. Immunoreactive relaxin levels were undetectable in the nonpregnant controls, whereas levels in both timed-pregnant controls and timed-pregnant affected mice were significantly higher than in nonpregnant controls, but not significantly different from each other. Mean interpubic ligament length in the pregnant Hertwig's anemia mice was significantly greater than that in nonpregnant controls, but significantly less than that in the pregnant controls on Day 18 of pregnancy. Porcine relaxin was administered to nonpregnant affected and unaffected littermates and to nonpregnant controls. Whereas controls showed a significant response to porcine relaxin, neither the Hertwig's anemia mice nor their unaffected littermates responded to the porcine relaxin. Additional study was performed to determine estradiol effects in the affected and control animals utilizing detailed computerized morphometric analysis of uterine horns and cervices from immature, estradiol-injected controls and Hertwig's anemia mice. Results demonstrated a statistically significant trophic effect of estradiol upon uterine horn and cervical enlargement, as assessed by weight and volume, in controls. Only a slight, non-significant effect was seen in Hertwig's anemia mice. Additional histological effects of estradiol, including endometrial enfolding observed in controls, were not present in Hertwig's anemia mice. Lack of response to both estrogen and relaxin is responsible for the parturitional defect in Hertwig's anemia mice.

Anemia, Macrocytic↗

Parapulpal pins and their effects on the fracture resistance of pin-retained cores.

The bending characteristics of various parapulpal pins, the retention of a parapulpal pin in different core buildup materials, and the fracture resistance of pin-retained cores were investigated in an in-vitro study. In amalgam and composite cores, the use of parapulpal pins produced an increase in fracture resistance. The highest fracture resistance values were observed in amalgam cores, and the lowest fracture strength was exhibited by cores of glass ionomer cements (GICs) containing metallic particles. The different parapulpal pins and their flexural rigidity had little effect on the fracture resistance of the pin-retained cores. For extensive pin-retained cores it appears advisable to use GICs with restraint and, particularly in the case of large-scale bridge reconstructions, only after critical examination of the loading conditions.

Alloys↗

Headache in HIV-1-related disorders.

To define the causes, clinical significance and characteristics of headaches in HIV-1-related disorders, we studied 49 consecutive HIV-1 infected patients who presented with headache. Work-up included CT scans, cerebrospinal fluid examinations (in the absence of a contraindication) and serologic studies. Overall, 40 of 49 patients (82 percent) had an identifiable serious cause of headache. Cryptococcal meningitis (39 percent) and CNS toxoplasmosis (16 percent) were the leading headache etiologies. Serious causes were more likely in patients diagnosed with AIDS prior to presentation but also occurred in most patients in early stages of infection. Based on this study, we suggest that patients with HIV-1 infection must be managed with a high index of suspicion when they present with new onset headaches.

Adult↗

Endothelin- and oxytocin-induced calcium signaling in cultured human myometrial cells.

The demonstration that endothelin (ET) induces rat uterine contraction, coupled with the observation that ET is present in human amniotic fluid, suggests that the myometrium may be an important target organ for this hormone. We show that in quiescent human myometrial cells ET produced a dose-dependent increase in cytosolic free Ca2+ (Cai2+), which was markedly attenuated when the cells were studied in Ca2(+)-free media. Preincubation with nicardipine, diltiazem, or verapamil reduced the ET-evoked Cai2+ transient by 30, 40, and 65%, respectively. The presence of voltage sensitive Ca2+ channels was demonstrated by Mn2+ quenching of fura-2. Activation of the Na+/H+ antiport could not be demonstrated with ET stimulation. In nonquiescent cells, the ET-evoked Cai2+ transient was significantly reduced, while the response to oxytocin was retained. This is at least partially explained by a reduction in Bmax (maximal binding capacity) for ET (mean +/- SEM) from 3,506 +/- 268 binding sites/cell in quiescent cells to 2,411 +/- 300 binding sites/cell, as well as 72% increase in Kd (equilibrium dissociation constant), in the nonquiescent cells. We conclude that, in human myometrial cells, ET and oxytocin modulate Cai2+ through independent receptors and propose that ET, like oxytocin, is an important endogenous modulator of uterine contractility.

Actins↗

A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma.

Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiring pressors (45%), dyspnea (36%), renal insufficiency (24%), hepatic dysfunction (66%), and cardiac arrhythmias (18%). These toxicities reversed with cessation of the infusion. There were four deaths during the first 30 days of treatment, three from infection (one related to central line, one related to LAK cells, one related to tumor), and one from tumor-related hemorrhage. Toxicity was unexpectedly high and at least comparable to that seen in previous studies using a high-dose IV bolus schedule of IL2. When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.

Adult↗

A phase I trial of taxol given by a 6-hour intravenous infusion.

Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

Alkaloids↗

Ovarian control of pituitary hormone secretion in early human pregnancy.

To determine the influence of ovarian relaxin on the secretion of pituitary GH and PRL in vivo, we evaluated circulating serum hormone levels in 17 pregnant patients with functional corpora lutea (group I) and compared them to levels in 10 patients with premature ovarian failure (POF; group II) who became pregnant with egg donation and did not have corpora lutea. Group II patients had exogenous hormonal support. Serum relaxin (RLX), GH, PRL, estradiol (E2), and progesterone levels were measured weekly by RIA from weeks 4-8 of pregnancy. Analysis of variance and covariance were used to determine hormonal relationships. Serum RLX was present in the natural pregnancy group, with a mean of 1.94 micrograms/L over the study period. Serum RLX was undetectable in the POF patients (less than 0.16 micrograms/L). No significant difference in PRL or progesterone levels between the two groups was noted. E2 levels showed an upward trend in both groups with time and were significantly higher in patients of the POF group than in group I women (P = 0.001). GH levels were significantly higher in the natural cycle patients (P = 0.02) despite lower E2 levels. These data provide additional support for the concept that RLX production in early pregnancy originates from the corpus luteum. They suggest that a luteal product, probably RLX, stimulates GH secretion in early pregnancy. This is a previously undescribed role for RLX in pituitary physiology during human pregnancy.

Adult↗

The death of Charlotte Brontë.

Although her own physician ascribed her death to tuberculosis, later evaluation of Charlotte Brontë's life and work led some observers to conclude that the cause of her death was hyperemesis gravidarum, a pregnancy complication that was ascribed to neurosis and a rejection of her pregnancy and her femininity. A full analysis of Charlotte Brontë's last months casts doubt as to whether she was ever actually pregnant. Evaluation of her final illness suggests that tuberculosis with secondary Addison disease can fully explain her terminal signs and symptoms.

England↗

Replication-linked histone acetylation in rat liver tissue is sensitive to alkylating agents.

The effect of alkylating agents on histone acetyltransferase (EC 2.3.1.48) activity and thymidine incorporation was investigated in benign and malignant proliferating rat liver tissue and compared with the effect in normal non-proliferating rat liver tissue. In both, benign and malignant proliferating tissue, but not in quiescent tissue, the histone acetylation is depressed by alkylating agents and this depression correlates with the inhibition of the thymidine incorporation. This effect suggests that the depression of the replication associated histone acetylation may be an important factor for the antiproliferative activity of alkylating agents.

Acetylation↗