Evaluation of transcutaneous bilirubinometry in preterm neonates.

OBJECTIVE: To determine the accuracy and precision of transcutaneous bilirubin (TcB) measurements in preterm neonates. STUDY DESIGN: Neonates were stratified into three groups on the basis of gestational age: 24 to 28 weeks (Group 1, n=30), 29 to 31 weeks (Group 2, n=29) and 32 to 34 weeks (Group 3, n=31). TcB was measured using the Draeger Air Shields JM-103, and when possible, measurements were made by two observers. TcB and total serum bilirubin (TSB) measurements were compared, and interobserver precision for TcB measurements was assessed. RESULT: Correlations between TcB and TSB ranged from 0.79 to 0.92. Most of the differences between TcB and TSB were +/-2 mg per 100 ml, and there was no trend for the difference to increase with increasing bilirubin values. Sensitivity, specificity and negative predictive values ranged from 0.67 to 1.0, 0.29 to 0.81 and 0.60 to 1.0, respectively. Intraclass correlations were 0.87 to 0.92. CONCLUSION: TcB correlates significantly with TSB in preterm neonates, and interobserver precision is significant. Routine measurement of TcB in preterm neonates may provide enhanced clinical monitoring for hyperbilirubinemia.

IGF-1 does not moderate the time-dependent transcriptional patterns of key homeostatic genes induced by sustained compression of bovine cartilage.

OBJECTIVE: To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with Insulin-like growth factor-1 (IGF-1) and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. METHODS: Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 h after compression +/-IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. RESULTS: IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24h compression suppressed this effect. Compression alone up-regulated expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 and transforming growth factor (TGF)-beta, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, tissue inhibitor of metalloproteinase (TIMP)-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated. CONCLUSION: Sustained compression markedly altered the effects of IGF-1 on expression of genes involved in cartilage homeostasis, while IGF-1 was largely unable to moderate the transcriptional effects of compression alone. The demonstrated co-expressed gene pairings suggest a balance of anabolic and catabolic activity following simultaneous mechanical and growth factor stimuli.

Nitric oxide enhances aggrecan degradation by aggrecanase in response to TNF-alpha but not IL-1beta treatment at a post-transcriptional level in bovine cartilage explants.

OBJECTIVE: The objective of this study was to determine the role of nitric oxide (NO) in tumor necrosis factor alpha (TNF-alpha)-induced matrix damage, compared to interleukin 1 beta (IL-1beta), in bovine cartilage explant cultures. METHODS: Cartilage explants were subjected to treatment with TNF-alpha (100ng/ml), IL-1beta (10 ng/ml) and to the nitric oxide synthase inhibitor, N-methyl-arginine (L-NMA; 1.25 mM) for 26, 50 or 120 h (5 days). The collected medium was analyzed for sulfated glycosaminoglycan (sGAG), nitrate and nitrite, matrix metalloproteinase (MMP) activity by zymography, and aggrecan degradation by immunoblotting of aggrecan-G1 and aggrecan-G1-NITEGE fragments. RNA was extracted from the 26 and 50 h treated explants for real time quantitative PCR analyses. RESULTS: TNF-alpha and IL-1beta treatment caused a 3-5 fold increase in sGAG release with an increase in aggrecanase-specific aggrecan breakdown and an increase in nitrate and nitrite production. L-NMA treatment inhibited almost 50% of the sGAG release caused by TNF-alpha treatment, with concomitant decrease in the aggrecanase-specific-NITEGE neo-epitope of aggrecan released into the medium. No L-NMA effect was identified with IL-1beta. TNF-alpha and IL-1beta both increased a disintegrin and matrix metalloproteinase with thrombospondin motif (ADAMTS)4 and ADAMTS5 transcription with no effect by L-NMA, suggesting that NO regulates aggrecanase activity at a post-transcriptional level in response to TNF-alpha. TNF-alpha and IL-1beta both caused an increase in protease transcription (MMP-3, MMP-13, ADAMTS4 and ADAMTS5) and in pro-inflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase (COX)-2, as well as a decrease in matrix protein transcription, including collagen II, aggrecan, fibromodulin and link protein (IL-1beta only), and an increase in MMP-3 and MMP-9 secretion. L-NMA had no effect on gene transcription or MMP secretion. CONCLUSION: NO regulates aggrecanase activity at a post-transcriptional level in response to TNF-alpha treatment while having no effect on IL-1beta treated cartilage explants.

A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients.

This randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 micrograms/kg/d in combination with Filgrastim at 10 micrograms/kg/d or Filgrastim alone at 10 micrograms/kg/d, from 203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34(+) cell target yield. There was a clinically and statistically significant reduction (P <.05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie, <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation.

Prevention and management of omental herniation after laparoscopy.

Omental herniation through laparoscopic cannula sites is an uncommon but serious complication of laparoscopy. Its frequency will probably increase as more and different types of endoscopic surgery are performed. Omental herniation occurred in two women and was corrected under local anesthesia.

Predicting probabilities of pregnancy and multiple gestation from in vitro fertilization--a new model.

OBJECTIVE: To develop a statistical model that adjusts for variation between patients and adequately predicts the observed distribution of pregnancies among singletons and multiple gestations of various orders. METHODS: All in vitro fertilization (IVF) cycles from the inception of the IVF program at Women and Infants' Hospital on May 26, 1988, until December 31, 1993, were evaluated using logistic regression in selected subsets. RESULTS: A new cycle-one specific model uses three different probabilities: P1, the probability of pregnancy (predicted by age and total embryo score); P2/P1, the conditional probability of finding a second implantation in those who had become pregnant with at least one (predicted by total embryo score); and P3/P2, the conditional probability of finding a third implantation in those who had become pregnant with at least two (with no significant predictors). This is the first model to use these three adjusted probabilities. CONCLUSION: P1 increases with increasing total embryo score but decreases with increasing age. P2/P1 increases with increasing total embryo score but does not depend on age. Embryo scoring is useful because the total embryo score is a better predictor of P1 and P2/P1 than the number of embryos alone. By using patient-specific information (age and total embryo score) and cycle-specific tables, an estimate of the probability of pregnancy and multiple gestation can be provided before embryo transfer.

The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.

OBJECTIVE: To determine the impact of hydrosalpinx on pregnancy rates in patients undergoing IVF for infertility caused by tubal disease. DESIGN: Review of the records of all patients who had undergone IVF for tubal factor infertility at our institution between May 1988 and October 1994. SETTING: A university-sponsored, hospital-based IVF facility. PATIENT(S): Two hundred fifty patients were identified with infertility due to tubal disease; 67 of these had at least one documented hydrosalpinx whereas the remaining 183 did not. MAIN OUTCOME MEASURE(S): Numbers of oocytes retrieved and fertilized, the number of embryos transferred and implanting, and resulting pregnancy rates. RESULT(S): The groups were similar in age and cycle cancellation rates. The patients with hydrosalpinx had greater numbers of oocytes retrieved per cycle (15.0 versus 11.6) and embryos transferred per cycle then those without hydrosalpinges (4.21 versus 3.98). The hydrosalpinx group also undertook more cycles per patient (2.31 versus 1.96). Fertilization rates between the two groups were similar, but implantation rates were decreased in those with hydrosalpinx (8.5% versus 11.2%). CONCLUSION(S): Hydrosalpinx did not result in impaired ovarian stimulation or decreased oocyte fertilization. It did, however, interfere with implantation and reduce to some degree the success of IVF in achieving an ongoing pregnancy. The validity of routine salpingectomy for hydrosalpinx is debatable, but its use in selected individuals may well be appropriate.

Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies.

OBJECTIVE: To determine the effects of multifetal reduction and other variables on the duration of gestation of in vitro fertilization (IVF) pregnancies. METHODS: All 274 IVF pregnancies from the inception of the Women and Infants' Hospital IVF Program on May 26, 1988, until December 31, 1993, were evaluated. RESULTS: Spontaneous reduction occurred in ten pregnancies, and multifetal reduction was elected in 28 multiple gestations. Among 260 pregnancies that remained viable beyond 20 weeks, 162 singletons (37.9 +/- 0.29 weeks; mean +/- standard error) had a longer mean gestation than did 64 twins (34.6 +/- 0.61 weeks), 25 pregnancies reduced to twins (33.4 +/- 1.0 weeks), or nine triplets (29.7 +/- 1.9 weeks). Triplets delivered 4.9 weeks earlier than nonreduced twins (P < .05) and 3.7 weeks before twins resulting from multifetal pregnancy reduction (P < .05). Regression analysis showed that at the 8-week ultrasound, each viable fetus could be expected to reduce the duration of the gestation by about 3.6 weeks, and each fetus reduced medically or as a result of natural causes could be expected to prolong the gestation by approximately 3.0 weeks. Only 14% of triplet pregnancies underwent spontaneous multifetal reduction. CONCLUSION: Multifetal reduction of pregnancies with three or more fetuses was beneficial and increased the duration of gestation.

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN AND METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage--colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU-GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G-CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.

Premature ovarian failure: treatment strategies.

Premature ovarian failure is a relatively common condition whose diagnosis, despite several known etiologies, most often results from an unknown cause. Treatment options for the women not desirous of pregnancy are straightforward and consist of hormone replacement therapy. For the patient who hopes to attain a pregnancy, treatment is much more complex and has, in the past not held much promise. However, with the advent of the use of donor oocytes, an extremely effective option is available.

Development of a neonatal intensive care nursery resuscitation and triage team: impact on nursing care and infant outcome.

The admission and initial stabilization of an infant in the neonatal intensive care unit pose a time of increased stress for the neonate as well as the caregivers. Constant observation by nursing personnel is critical so that major physiologic and anatomic changes that naturally occur do not compromise the neonate during this time of extrauterine adjustment. Continuous reassessment of temperature, respiration, heart rate, blood pressure, color, tone, and behavior during the initial four-hour postnatal period is crucial for the infant's survival and the preservation of an intact central nervous system and cardiopulmonary function. The complexity of the admission process should not jeopardize the nursing care of other infants in a busy neonatal intensive care unit. We developed a framework that separates bedside nursing activities from the resuscitation and admission process that ensures the infant's transition to the nursery is met with urgency and consistency without subjecting the remaining infants to a decreased level of care.

Early and late presentation of the ovarian hyperstimulation syndrome: two distinct entities with different risk factors.

This study was designed to identify clinical predictors for early and late ovarian hyperstimulation syndrome (OHSS). A retrospective analysis of all 592 in-vitro fertilization (IVF) cycles from the programme's inception in 1988 up to March 1993 was performed. Six patients (1.0% of cycles) had moderate or severe OHSS presenting 3-7 days post-human chorionic gonadotrophin (HCG), and four patients (0.7% of cycles) had severe OHSS presenting 12-17 days post-HCG. No patient with early OHSS went on to develop late OHSS, and no patient with late OHSS had demonstrated early OHSS. Stepwise logistic regression showed that early OHSS was predicted by the number of oocytes retrieved (range 18-46) (P = 0.0001) and the oestradiol concentration on the day HCG was given (range 12,122-24,454 pmol/l) (P = 0.0003). Late OHSS was predicted by the number of gestational sacs (range 2-3) on ultrasound 4 weeks after embryo transfer (P = 0.0001) but not by the number of oocytes or oestradiol. Early OHSS was an acute effect of the HCG administered prior to egg retrieval in women with high oestradiol and larger numbers of follicles (range 22-51). Late OHSS was induced by the rising serum concentration of HCG produced by the early pregnancy, and in this series of cases it was associated only with multiple gestation.

Dehydroepiandrosterone sulfate and anovulation increase serum inhibin and affect follicular function during administration of gonadotropins.

To test the hypothesis that testosterone (T) derived from circulating dehydroepiandrosterone sulfate (DS) or produced in excess within the anovulatory ovary is a follicular regulator capable of stimulating inhibin secretion. DS and inhibin were determined by RIA in residual serum samples from in vitro fertilization cycles and analyzed along with other parameters using analysis of variance and stepwise multiple linear regression after log transformation of the RIA data. It was predicted that the serum concentration of inhibin would be higher in women with anovulation than in normal subjects and that the serum inhibin concentration would have a positive regression coefficient on the serum DS concentration. The serum concentrations of inhibin (P < 0.01) and estradiol (P < 0.001) on the day of hCG treatment were higher in women with anovulation than in normal subjects, as was the number of oocytes retrieved (P < 0.001). The FSH and LH doses (both P < 0.005) and age (P < 0.001) were significantly lower, and the average duration of gonadotropin therapy was 1 day shorter (P < 0.001) in anovulatory patients. There was no significant difference in serum DS (P > 0.2). Regression analysis showed that serum inhibin was positively related to the number of oocytes (P < 0.001) and serum DS (P = 0.05), with an increase in anovulatory subjects (P < 0.025). The duration of treatment with gonadotropins was related positively to the patient's age (P < 0.001) and negatively to serum DS (P < 0.025), with a decrease in anovulatory subjects (P < 0.025). The number of oocytes obtained was negatively related to age (P < 0.001) and positively to serum DS (P < 0.005). These data are consistent with a stimulatory effect of follicular T derived from either circulating DS or the anovulatory ovary, which affects the secretion of inhibin, the duration of gonadotropin treatment, and the number of oocytes retrieved.

Topical ocular anesthetics in ocular irritancy testing: a review.

The routine use of topical anesthetics to alleviate discomfort associated with in vivo ocular irritancy testing has been advocated. This review provides information about the adverse effects of topical ocular anesthetics and answers the questions: are topical anesthetics practical and effective in ocular irritancy protocols, is long-term use contraindicated, will topical anesthetics alter the response of a test substance, and are there significant side-effects which might cause pain and suffering in test animals? There was no evidence to support the use of a specific topical anesthetic. Further, information about using systemic analgesics or combinations with local anesthetics that would effectively alleviate discomfort associated with ocular irritancy testing without affecting test results was not found. Comprehensive studies are needed to identify the most effective combination of drugs that would ameliorate discomfort associated with ocular irritation testing.

Anterior uveal melanoma, with secondary keratitis, cataract, and glaucoma, in a horse.

Intraocular melanoma was diagnosed in a 13-year-old horse. Secondary clinical findings included keratitis, cataract, and glaucoma. The eye was enucleated. Follow-up information did not give an indication of metastatic disease.

Cisplatin, continuous-infusion 5-fluorouracil, and intermediate-dose methotrexate in the treatment of unresectable non-small cell carcinoma of the lung.

Forty-one patients with unresectable non-small cell carcinoma of the lung (NSCCL) were treated with cisplatin 20 mg/m2/d for 5 days as a daily bolus injection, 5-fluorouracil 800 mg/m2/d by continuous infusion for 5 days, and intermediate-dose methotrexate 200 mg/m2 on days 15 and 22 of a 28-day cycle (PFM). One complete and 23 partial responses were observed, yielding an overall response rate of 60%. There was no significant difference in response rates based on histologic subtype or extent of disease (locally unresectable versus metastatic). Median duration of response was 6 months, and the median survival of all patients was 10 months. Two patients with unresectable disease at presentation became resectable after chemotherapy and remain disease-free at 46+ and 53+ months. Toxicity was modest, with oral mucositis the major adverse effect. Clinically important neutropenia was uncommon. PFM is an active regimen in NSCCL and deserves further study in the "neoadjuvant" setting.