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Biomedical subjects

R T Scott

Publications and source records attributed to R T Scott.

89 records · Page 5Linked to original sources

Critical assessment of sperm morphology before and after double wash swim-up preparation for in vitro fertilization.

Critical assessment of sperm morphology using specific and stringent criteria is predictive of the subsequent ability of those sperm to fertilize oocytes in in vitro fertilization (IVF). Previous studies have evaluated sperm morphology prior to sperm preparation and, thus, have not assessed the actual sperm used for insemination. We studied the impact of a double wash swim-up technique used for IVF on sperm morphology using the strict criteria of Kruger et al. [5, 6] in 73 consecutive patients undergoing IVF. Pre- and postswim-up morphological assessments were done in a prospective, randomized, and blinded fashion. The mean percentage of normal forms pre- and postswim-up was 19.8% and 23.4%, respectively, an improvement of 18% (p less than 0.05) with 62 of 73 patients showing improvement. Significantly, analysis of the 27 patients with abnormal morphology on initial assessment (normal forms less than or equal to 14%) revealed an improvement in percentage of normal forms from 9.0% to 21.5%, a mean increase of 239% (p less than 0.005). Eighteen of these 27 patients showed improvement in their percentage of normal forms, eight were unchanged, and only one patient had a decline in their percentage of normal forms. We conclude that the double wash swim-up preparation used for IVF substantially improves the percentage of sperm with normal morphology, and that the benefit is most substantial in those cases where the percentage of normal morphology is abnormal.

Fertilization in Vitro↗

Ovulation induction for assisted reproduction.

The goal of ovulation induction in assisted reproduction is the development of multiple follicles, allowing the recovery of multiple mature, high-quality oocytes. Normally ovulatory women may respond very differently to gonadotropin stimulation. Most patients respond best to regimens that provide the highest quantities of gonadotropins in the early follicular phase followed by tapering dosages as the gonadotropin requirements of the developing follicles are reduced. Others, particularly those with inverted luteinizing hormone:follicle-stimulating hormone ratios, respond better to constant, low-dose, pure follicle-stimulating hormone protocols. Patients with elevated basal follicle-stimulating hormone concentrations may require upwards of eight ampules of gonadotropins per day to obtain multifollicular development. Gonadotropin releasing hormone agonists are of value in patients with exaggerated multifollicular responses as well as in those who have premature luteinizing hormone surges. In all cases, optimization of ovulation induction through the customization of stimulation regimens results in improved stimulation quality and outcomes.

Chorionic Gonadotropin↗

Maternal height and weight gain during pregnancy as risk factors for cesarean section.

Maternal height, maternal weight, infant weight, and maternal weight gain during pregnancy were examined as factors associated with the likelihood of delivery by cesarean section for cephalopelvic disproportion (CPD). Sixty-four women, delivered by cesarean section for CPD, were compared with matched controls who delivered vaginally. The only factor associated with an increased risk of cesarean section for CPD was short stature: women shorter than 63 inches were 4.9 times more likely to have CPD than taller women.

Adult↗

Validation of the hemizona assay in a monkey model: influence of oocyte maturational stages.

The hemizona assay (HZA) was used in the monkey model to investigate sperm binding to the zona pellucida and to evaluate binding patterns according to various stages of oocyte development. Adult cynomolgus monkeys were superovulated with human menopausal gonadotropin. The oocytes were retrieved by laparoscopy, stored in salt solution, then cut into hemizonae by micromanipulation. Metaphase II oocytes showed significantly tighter binding than prophase I oocytes (P less than 0.001). Metaphase I oocytes showed intermediate binding, significantly different from the other groups (P less than 0.01). It is concluded that: (1) This study demonstrates the feasibility of HZA as a test to evaluate sperm/zona interactions in the monkey, using standards reported for human studies. (2) Oocyte meiotic competence seems to be accompanied by an increase in zona-binding properties.

Animals↗

The effect of interobserver variation in dating endometrial histology on the diagnosis of luteal phase defects.

Endometrial biopsy specimens (n = 62) were evaluated by five pathologists to assess the effect of interobserver variation on histologic dating of the endometrium. The potential effect of this variation on the diagnosis of luteal phase defects (LPDs) and resulting clinical management was also determined. Mean (+/- standard error) interobserver variation was 0.96 +/- 0.08 days, comparable to results reported by other investigators. The magnitude of the variation was not affected by whether the biopsy specimen was obtained in the mid or late luteal phase, the degree of lag between the dating and subsequent menses, or the presence of an LPD. Redating of a specimen by another pathologist would have resulted in a change in the determination of "in" or "out" of phase in 22% of cases. The subsequent probability of changing patient management altered ranged from 22% to 39% depending on the clinical setting.

Endometrium↗

Maternal arterial desaturation with 15-methyl prostaglandin F2 alpha for uterine atony.

Over a six-month period, five women with severe uterine atony and postpartum hemorrhage developed marked maternal arterial oxygen desaturation within five to ten minutes of the administration of 15-methyl prostaglandin F2 alpha. The average fall from baseline was 10.4 +/- 5.4%, to a mean arterial oxygen saturation of 88.8 +/- 5.45%. The desaturation was accompanied by acute increases, averaging 20.7 +/- 5.9%, in the intrapulmonary shunt.

Blood Gas Analysis↗

Characterization of acyclovir-resistant and -sensitive herpes simplex viruses isolated from a patient with an acquired immune deficiency.

Several different genital and non-genital HSV isolates were obtained from a patient with an acquired immune deficiency of unknown aetiology. The patient was initially treated with topical acyclovir (ACV) and later with topical and intravenous ACV. In spite of treatment with antiviral drugs the patient continued to shed virus and to have extensive genital ulcerations. Restriction endonuclease (RE) analyses of the viral DNA revealed that all the isolates had characteristic HSV-2 patterns and that there were three genetically distinct virus groups among the ten isolates tested. Three post-therapy isolates, with the same RE pattern, were found to be devoid of thymidine kinase activity (TKD), highly resistant to ACV in cell culture, but sensitive to vidarabine (ara-A), phosphonoacetate and phosphonoformate. Two of these TKD isolates were obtained during and after topical ACV therapy and before intravenous treatment. Mice inoculated intracerebrally with a lethal dose of each of the three TKD viruses were refractory to ACV, but responded to vidarabine or a combination of ACV and ara-A. Mice inoculated with the TK+ viruses (including the pre-therapy isolate) responded to ACV and/or ara-A treatment. The results indicate that: (i) TKD variants may be produced in humans after topical ACV therapy; (ii) different ACV-resistant or sensitive HSV-2 variants can establish latency at different body sites and reactivate; and (iii) when drug-resistant viruses are isolated from patients with multiple reactivations, the drug in question should not be discontinued, since the patients may also be shedding drug-sensitive virus at a different body site.

Acquired Immunodeficiency Syndrome↗

Delayed treatment with combinations of antiviral drugs in mice infected with herpes simplex virus and application of the median effect method of analysis.

Mice were inoculated intracerebrally with a lethal dose of herpes simplex virus type 2. Three days later, the mice were treated intraperitoneally, twice daily for 4 days, with the following drugs alone or in combination: acyclovir (ACV), vidarabine (ara-A), 2'-fluoro-5-iodoaracytosine (FIAC), and 2'-fluoro-5-methylarauracil (FMAU). Despite delayed treatment, most of the animals receiving low doses of FMAU alone or in combination with ACV or ara-A survived. In contrast, significantly higher mortality rates were noted in mice receiving ara-A, ACV, or FIAC alone. The data were analyzed for quantitation of synergism, additivity, and antagonism of multiple drug effect by the median effect method. The median effective doses (in nanomoles per kilogram per day) calculated in this manner were: FMAU, 22.5; FIAC, 510; ara-A, 901; ACV, 7,587; ACV-ara-A (drug ratio, 1:1), 550; FIAC-ara-A (1:1), 376; FIAC-ACV (1:1), 133; FMAU-ACV (1:8), 60.3; and FMAU-ara-A (1:8), 65.2. Marked synergy was found throughout a wide range of effect levels with the five different combinations, with no increased toxicity over the single-drug treatments. Similar results were obtained when the data were analyzed by the isobologram method. Since many patients with severe herpetic infections, such as herpes encephalitis, have a poor prognosis despite single-drug therapy, the possible use of combinations including low doses of FMAU deserves further investigation.

Animals↗

Medical aspects of drug misuse during one year in a rehabilitation unit.

The medical work in a voluntary drug rehabilitation unit near Glasgow was examined. During one year 174 residents were admitted of whom 103 (59%) developed illnesses which required medical treatment. The need for drug misusers to receive general medical services during and after drug misuse was confirmed. Although withdrawal from barbiturate misuse required the prescription of controlled drugs, opiate and other withdrawals were satisfactorily managed with psychological support and general care; substances which could be abused were not prescribed. Blood testing of 129 residents showed that 114 (88%) had evidence of previous hepatitis B infection, while only two had human immunodeficiency virus (HIV) antibody. The low prevalence of HIV antibody compared with the high prevalence that has been reported in Edinburgh suggests that the opportunity exists at the moment to limit the spread of acquired immune deficiency syndrome among Glasgow drug misusers.

Adolescent↗

Antiviral activity of 5-ethyl-2'-deoxyuridine against herpes simplex viruses in cell culture, mice, and guinea pigs.

The susceptibility of 3 laboratory strains and 24 clinical isolates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) to 5-ethyl-2'-deoxyuridine was determined in plaque reduction assays in Vero cells. The median effective doses were 8.6 and 7.8 microM, respectively. The drug was less potent than acyclovir and other related antiviral drugs, but it had a high therapeutic index against both HSV-1 and HSV-2. Drug-resistant viruses were readily produced in cell culture. These variants were cross-resistant to acyclovir, 2'-fluoro-5-iodoaracytosine, and 2'-fluoro-5-methylarauracil but were susceptible to vidarabine or phosphonoformate. These findings confirm that the selective antiviral activity of 5-ethyl-2'-deoxyuridine is mediated by the virus-induced thymidine kinase. Oral or intraperitoneal administration of the drug at nontoxic doses was ineffective in protecting mice against intracerebral challenge with virus. Using implanted osmotic minipumps or coadministering the drug with dimethyl sulfoxide failed to decrease the mortality rate. In guinea pigs infected genitally with HSV-2, topical drug treatment was more effective than placebo in reducing lesion severity and other clinical and virological variables. These effects were noted whether the drug treatment was initiated 3 or 24 h after infection (ascertained serologically). Drug-treated animals had a significantly lower herpes antibody titer than did placebo-treated guinea pigs, suggesting that the drug can also reduce the viral antigen load. In this model, the drug appeared to be as effective as topical phosphonoformate or acyclovir.

Animals↗

Metabolic coma.

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Adult↗

Creatine kinase and creatine kinase isoenzymes as a marker of uterine activity.

Creatine kinase (CK) and CK isoenzymes are known to fluctuate in labor. Reliable information about the longitudinal changes of CK and CK isoenzymes during labor is sparse. Nevertheless, they have been used to direct care in women with cardiopulmonary disease and preterm labor requiring tocolysis. This study evaluated fluctuations of CK and its isoenzymes longitudinally across labor in 49 women. Blood samples were obtained at 33 to 34 weeks' estimated gestational age, on admission in labor at 3 cm or less dilation, 8 cm to complete dilation, and postpartum in the recovery room. Specimens were analyzed for total CK, CK-MM, CK-MB, and CK-BB activity. CK levels increased for all peripartum patients (p < 0.001). CK activity at 3 cm was greater than at 34 weeks (p < 0.01). Furthermore, the early rise in CK activity was greater in those in active labor compared with those who required oxytocin stimulation (p < 0.001). CK values at 8 cm and postdelivery (mean IU/liter) were often above nonpregnant norms. The early rise of CK in spontaneously laboring patients versus those requiring oxytocin augmentation may represent a difference in uterine activity. Nonpregnant normative data for CK is not appropriate when assessing cardiovascular side effects of betamimetic therapy.

Biomarkers↗

In vivo effects of a potent GnRH antagonist ORG 30850: physiologic evidence that down-regulation of GnRH receptors does not occur.

OBJECTIVE: Our purpose was to determine the pituitary responsiveness to exogenous GnRH in GnRH antagonist-suppressed ovariectomized monkeys. METHODS: This was a prospective experimental non-human primate study performed at the research laboratories of The Jones Institute for Reproductive Medicine. Seventeen long-term ovariectomized cynomolgus monkeys were studied. INTERVENTIONS: The GnRH antagonist ORG 30850 was administered to long-term ovariectomized monkeys assigned to one of six groups: single subcutaneous injections in group A (n = 4), 0.3 mg/kg; group B (n = 4), 1.0 mg/kg; and group C (n = 3), 3.0 mg/kg; and six consecutive daily subcutaneous injections in group D (n = 2), 0.3 mg/kg; group E (n = 2), 1.0 mg/kg; and group F (n = 2), 3.0 mg/kg. Blood samples were collected daily from 10 days before treatment until 22 days after treatment, then weekly for 6 additional weeks. Intravenous GnRH stimulation tests (10 micrograms/kg) were performed on the day after vehicle injection (control) and the day after completion of treatment(s), and then at weekly intervals. The main outcome measures were serum levels of LH, FSH, and ORG 30850. RESULTS: Administration of ORG 30850 resulted in suppression (P < .05) of LH and FSH in all treatment groups. Long-term suppression (greater than 2 weeks) was evident in all primates receiving a cumulative dose of at least 1 mg/kg. Paradoxically, the responsiveness of the pituitary to exogenous GnRH was accentuated during the time of maximal tonic LH/FSH suppression. CONCLUSIONS: ORG 30850 is a potent long-acting GnRH antagonist. Furthermore, the present in vivo demonstration of heightened pituitary responsiveness to exogenous GnRH emphasizes the divergent mechanisms of action of GnRH antagonists and GnRH agonists.

Animals↗

Common technical errors in hysterosalpingography.

Hysterosalpingograms from 100 consecutive patients referred for in vitro fertilization were reviewed to evaluate the adequacy of visualization of the uterine cavity. In 17 cases the hysterosalpingogram failed to demonstrate the entire uterine cavity. The most common reason for failure was an axial view of the uterus secondary to inadequate traction on the cervix in 82% (14/17) of the cases, followed by obstructed visualization of the lower uterine cavity and endocervical canal by the delivery catheter bulb in 21% (3/17). A speculum left in the vagina obscured visualization of the endocervical canal in 21% (3/17) of the cases. There were no significant differences in the mean number of radiographic exposures between the adequate and inadequate groups (4.7 vs. 5.9). This study suggests that failing (1) to remove the speculum before injecting contrast, (2) to evaluate the lower uterus and endocervix when using an intrauterine catheter, or (3) to place adequate traction on the cervix, may result in inadequate visualization of the uterine cavity and a need to repeat the study.

Diagnostic Errors↗