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Biomedical subjects

M Lane

Publications and source records attributed to M Lane.

At least 37 records · Page 2Linked to original sources

Selection of viable mouse blastocysts prior to transfer using a metabolic criterion.

The success rate of human in-vitro fertilization (IVF) remains low, with only approximately 10% of embryos transferred resulting in a term pregnancy. A major contributor to this embryonic loss is poor embryo development in vitro. Such poor development can be attributed to both chromosomal and anatomic anomalies in oocytes after ovarian stimulation and to suboptimal embryo culture conditions. The low success rate of IVF is compounded by an inability to select those embryos most likely to implant after transfer (viable). Currently morphology is used almost exclusively as the sole criterion to decide which embryos are replaced. This procedure is not only subjective but has a poor correlation with subsequent developmental competence. Therefore, the development of techniques to quantify embryo viability prior to transfer will significantly increase pregnancy rates. We report here that the non-invasive assessment of glycolytic activity (percentage of glucose converted to lactate) in individual mouse blastocysts prior to transfer can be used successfully to identify viable embryos. Blastocysts with a low glycolytic activity, close to that of in-vivo developed blastocysts, had a significantly higher viability than those with abnormally elevated levels of glycolysis. Using glycolytic activity as a marker of viability resulted in a four fold increase in the pregnancy rate compared with embryos selected at random for transfer. We propose that the success of clinical IVF can be increased significantly by employing quantitative tests for viability.

Animals

Removal of embryo-toxic ammonium from the culture medium by in situ enzymatic conversion to glutamate.

An enzymatic method for removing embryo-toxic ammonium from culture medium has been developed. Ammonium, produced by both embryo metabolism and spontaneous breakdown of amino acids at 37 degrees C, is transaminated by glutamate dehydrogenase to nontoxic glutamate. Initially, the individual components of the transamination reaction were titrated against mouse embryo development in vitro to determine embryo-safe levels. ADP, an allosteric activator of glutamate dehydrogenase, was found to inhibit embryo development and was therefore omitted from the final formulation (alpha-ketoglutarate, 0.44 mM; glutamate dehydrogenase, 0.375 U; NADH, 0.12 mM). It was found that 0.30 mM ammonium could be removed from the culture medium in situ in 3 h. In situ removal of ammonium significantly increases both blastocyst cell number, implantation, fetal development, and fetal weight after transfer. Removal of ammonium by the conventional method of renewing the culture medium also increased blastocyst cell number but did not affect postimplantation development. In conclusion, it is possible to alleviate the toxic effects of ammonium in vitro on pre- and postimplantation mouse embryo development by its transamination in situ, thereby facilitating the continual exposure to embryo-derived factor(s) which stimulates both pre- and postimplantation development.

Animals

Breast cancer screening: racial/ethnic differences in behaviors and beliefs.

Racial/ethnic differences in breast cancer screening behaviors and beliefs were examined in 259 asymptomatic women, 50 years old or older, who participated in a no-cost worksite breast cancer screening program. Hispanics were more likely than African Americans to report having had mammography in the past year. Caucasians and Hispanics were more likely than African Americans to report having had a clinical breast examination in the past year. African Americans to report having had a clinical breast examination in the past year. African Americans and Hispanics were more likely to practice monthly breast self-examination than were Caucasians. African Americans were more likely to report cancer-related fears and worries as barriers to mammography, whereas Caucasians were more likely to report being too busy, inconvenience, and procrastination as barriers. African Americans also were more likely to evaluate their physicians and other health professionals positively than were Caucasians. These results suggest a need to make a special effort to address cancer-related fears as barriers to screening among African Americans, and time-related barriers to screening among Caucasians.

Black or African American

The Gross Motor Performance Measure: validity and responsiveness of a measure of quality of movement.

BACKGROUND AND PURPOSE: This article presents the results of a study to validate a measure of gross motor performance for its capacity to detect changes in the quality of movement in children with cerebral palsy aged 0 to 12 years. SUBJECTS AND METHODS: On two occasions, 4 to 6 months apart, physical therapists from three children's treatment centers assessed 106 children with cerebral palsy, 18 children who had sustained an acute head injury, and 29 nondisabled children. Validity was demonstrated by comparing changes on the measure across diagnoses, severity, and age groups. RESULTS: Several a priori hypotheses were supported; however, relationships with parent and therapist ratings were not clearly demonstrated. CONCLUSION AND DISCUSSION: The measure was found to be differentially responsive to changes in "stable" and "responsive" groups.

Analysis of Variance

Cerebral palsy.

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Cerebral Palsy

Subtypes of psychosocial adjustment to breast cancer.

By means of cluster analytic techniques, four subtypes of psychosocial adjustment were identified in a sample of 122 breast cancer patients who completed the Psychosocial Adjustment to Illness Scale. Internal consistency and internal validity of the derived typology were suggested by the finding that two different hierarchical agglomerative clustering methods (average linkage between groups, Ward's) produced similar solutions. Three of the derived subtypes reported normal affect levels but different patterns of relative strengths and dysfunctions, while the fourth subtype appeared to be highly distressed and globally maladjusted. External validation was demonstrated by differentiating the subtypes on variables of negative affect, avoidance coping, and fighting spirit. The clinical and heuristic implications of these findings are discussed. The findings highlight the need for comprehensive assessment of psychosocial functioning of cancer patients. They demonstrate that even non-emotionally distressed patients can have very different profiles of adjustment and may benefit from correspondingly individually tailored psychosocial interventions.

Adaptation, Psychological

Training users in the gross motor function measure: methodological and practical issues.

BACKGROUND AND PURPOSE: The Gross Motor Function Measure (GMFM) is a criterion-referenced observational measure for assessing change in gross motor function for children with cerebral palsy (CP). The purposes of this report are to present data on the effects of training pediatric developmental therapists to administer and score the GMFM and to discuss some practical and methodological issues associated with training. SUBJECTS AND METHODS: A weighted kappa estimate pretraining and posttraining workshop was used to determine participants' agreement of scoring a videotaped GMFM assessment against experts' scoring of the same videotaped assessment. Several children with CP, representing a spectrum of ages, severities, and levels of function, were shown on the videotape. RESULTS: There was a significant improvement in agreement from a mean kappa of .58 to .82 (t = 15.38, df = 75, P < .001) for the first group and from .81 to .92 (t = 10.91, df = 72, P < .001) for the second group following training. CONCLUSION AND DISCUSSION: Although there are a number of advantages to using videotapes to train test users and to assess scoring reliability, this method does not evaluate participants' ability to administer the measure. Further work is needed to determine whether reliability is maintained in a clinical situation in which it is necessary to both administer and score the GMFM.

Adolescent

Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells: amino acids, vitamins, and culturing embryos in groups stimulate development.

The aim of this study was to develop a serum-free culture system that could support high levels of cleavage and blastocyst formation from sheep zygotes developed in vitro. To this end, we investigated the effects on sheep zygote development of amino acids, ammonium, vitamins, and culture of embryos in groups in Synthetic Oviduct Fluid (SOF) medium supplemented with BSA (32 mg/ml). The inclusion of amino acids in the culture medium had no effect on the percentage of embryos arrested at the 8-16-cell stage when embryos were cultured singly in the same drop of medium for 6 days (43% in SOF; 41% in SOF+amino acids). However, in medium containing all Eagle's amino acids, replacing the culture medium every 48 h to alleviate ammonium toxicity significantly decreased the number of arrested embryos (6%; p < 0.05) and significantly increased blastocyst cell number (52 cells in SOF; 105 cells in SOF+amino acids; p < 0.01) and the number of embryos developing to the blastocyst stage (29% in SOF; 67% in SOF+amino acids; p < 0.05). When the medium was renewed every 48 h, nonessential amino acids and glutamine also significantly decreased the number of arrested embryos (p < 0.05). Culturing embryos singly or in groups in SOF medium with all Eagle's amino acids that was renewed every 48 h resulted in significant increases in blastocyst hatching and mean cell number (47%, 31%, and 79%; 105, 136, and 173 cells for embryos cultured singly, in groups of 2, and in groups of 4, respectively). After culture in groups of 4, blastocyst cell numbers were equivalent to in vivo-developed controls (160 cells) and significantly greater than those developed in serum (103 cells; p < 0.01). Analysis of blastocyst metabolism, expressed on a per-cell basis, revealed that amino acids did not affect either glucose uptake or lactate production, whereas the addition of amino acids and vitamins resulted in a significant increase in both parameters (p < 0.01). A similar response was observed in serum-derived blastocysts. Ammonium production by sheep blastocysts after culture in the presence of amino acids was significantly greater than that produced by mouse blastocysts, indirect evidence that ruminant embryos utilize amino acids to a greater extent than do rodent embryos.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids

Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions.

The effects of amino acids and ammonium on the postimplantation development of cultured preimplantation mouse zygotes were assessed. Development after transfer revealed that the mouse embryo undergoes a switch in nitrogen requirements during the preimplantation period. Although Eagle's nonessential amino acids and glutamine supported the highest implantation and fetal development rates per embryo transferred when zygotes were cultured for 48 h, by 93 h of culture the highest implantation rate was observed when all 20 amino acids were in the culture medium. Furthermore, fetal development per implantation at 69 and 93 h of culture was increased only in the presence of essential amino acids without glutamine. The beneficial effects of amino acids on postimplantation development when embryos were cultured for 4 days required that the medium be renewed after 48 h (at the 6-8-cell stage) to alleviate the build-up of ammonium. Ammonium was shown to induce fetal retardation and exencephaly in a time- and concentration-dependent manner. Renewal of amino-acid-free culture medium reduced fetal mass, providing indirect evidence for the production of an embryo-derived growth factor capable of stimulating postimplantation development. These data demonstrate that inclusion of amino acids in the culture medium for preimplantation embryos significantly increases postimplantation development the preimplantation mouse embryo changes its nitrogen requirement as development proceeds, nonessential amino acids increase the implantation rate while the essential amino acids enhance fetal development, and ammonium in the medium retards fetal development and induces the neural tube defect exencephaly.

Amino Acids

Uptake and metabolism of pyruvate and glucose by individual sheep preattachment embryos developed in vivo.

The uptake of pyruvate and glucose by individual sheep oocytes and preattachment sheep embryos at each state of development up to the hatching blastocyst was determined using a microfluorescence technique. After an initial increase at fertilization, pyruvate uptake was relatively constant (approximately 15 pmol/embryo/h) from the zygote through to the morula. Upon blastocyst formation and hatching, there were significant increases in uptake (39 pmol/embryo/h, P < 0.001; and 53 pmol/embryo/h, P < 0.001, respectively). In contrast to that of pyruvate, glucose uptake was very low (approximately 1 pmol/embryo/h) up to the time of genome activation (eight- to 16 cell stage), after which there were significant increases in uptake at each successive stage of development. By the hatching blastocyst stage, glucose uptake had reached 54 pmol/embryo/h. The ability of day-7 hatching blastocysts to oxidize pyruvate and glucose was determined indirectly by measuring the production of lactate when either substrate was present as the sole energy source. Unlike the mouse blastocyst, which has a considerable oxidative capacity for both pyruvate and glucose, the day-7 sheep blastocyst showed limited ability to oxidise either substrate. Rather, in the sheep blastocyst, 65% of pyruvate and 98% of glucose taken up could be accounted for as lactate. Such low levels of substrate oxidation appear to be inconsistent with the energy requirements of the proliferating preattachment ruminant blastocyst. The utilization of alternative substrates at the blastocyst, such as amino acids, is proposed.

Animals

Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis.

The selective 5-hydroxytryptamine3 (5HT3) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose (> or = 100 mg/m2) cisplatin chemotherapy. A total of 125 patients were randomized (1:1:1) to receive 0.015, 0.15, or 0.30 mg/kg every 4 h for a total of 3 doses. All patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 h following cisplatin administration. The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes (P = 0.033) and complete response (no emetic episodes, P = 0.005). No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups. The most common adverse event was headache. Three 0.15-mg/kg doses of intravenous ondansetron are safe, effective, and adequate for the control of cisplatin-induced emesis.

Adult

Amino acids and ammonium regulate mouse embryo development in culture.

The regulation of 1-cell mouse embryo development in culture by amino acids was investigated. When the 20 amino acids in Eagle's medium were present, blastocyst formation at 72 h (9%; p < 0.01), and blastocyst cell number (66; p < 0.05) and hatching (45%; p < 0.05) after 96 h of culture were significantly increased, compared to control embryos grown in the absence of amino acids (0%, 60, and 23%, respectively). The beneficial effect of Eagle's amino acids was attributed primarily to the non-essential group. In the presence of non-essential amino acids, blastocyst formation (54%; p < 0.001) and cell number after 72 h of culture (33; p < 0.05), and blastocyst cell number (69; p < 0.01) and hatching (68%; p < 0.01) after 96 h of culture were all significantly greater than for embryos cultured with all amino acids (9%, 26, 66, and 45%, respectively). In the absence of glutamine, essential amino acids significantly reduced blastocyst cell number after 96 h (53; p < 0.05). Continual culture in the presence of amino acids reduced the cleavage rate after around 72 h of in vitro culture; this decrease was not observed in the absence of amino acids. Transfer of embryos to fresh medium after 48-72 h of culture resulted in increases in the percentage of blastocysts formed and in blastocyst cell numbers. These data are consistent with the build-up of an inhibitory compound in the medium, possibly ammonium, an end-product of amino acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

The relationship of dispositional optimism, daily life stress, and domestic environment to coping methods used by cancer patients.

The relationship of dispositional optimism, daily life stress, and domestic environment to two types of coping methods was examined in a group of 94 cancer patients. As expected, dispositional optimism and domestic environment made significant contributions to the prediction of avoidance coping. Dispositional optimism contributed significantly to the prediction of active-behavioral coping. Specifically, a significant positive relationship was obtained between active-behavioral coping and optimism. A significant positive relationship also was found between avoidance coping and both daily stress and domestic environment. Avoidance coping was negatively related to dispositional optimism. In multivariate analyses, gender and disease-related variables did not make significant contributions to the prediction of coping method. Suggestions for future research were made.

Adaptation, Psychological

Effect of incubation volume and embryo density on the development and viability of mouse embryos in vitro.

The morphology, cleavage rate and viability of preimplantation embryos from random bred Swiss mice were assessed after culture in different incubation volumes and embryo densities. Decreasing the incubation volume, from 320 to 20 microliters, significantly increased blastocyst cell number (P less than 0.01) and embryo development after transfer (P less than 0.01). Increasing the number of embryos incubated per drop from 1 to 16 significantly increased the number of two-cell embryos reaching the blastocyst stage in 5 or 320 microliters. Culturing embryos in groups significantly increased blastocyst cell numbers in all volumes employed and elevated embryo viability. Such observations are consistent with the hypothesis that the preimplantation mammalian embryo produces a factor(s) which can stimulate its own development. The results of this study have implications for clinical in-vitro fertilization, where embryos are routinely cultured individually in relatively large volumes.

Analysis of Variance

Duodenal ulcer relapse after eradication of Helicobacter pylori.

Thirty-six patients with healed duodenal ulcers, 27 infected with Helicobacter pylori and nine uninfected, were followed for up to 12 months to determine the rate of ulcer relapse. Eight patients withdrew over the follow up period. At one year, 15 of 20 (75%) infected patients and one of eight (13%) uninfected patients had relapsed, p less than 0.05. Eradication of H pylori favourably influences the natural history of duodenal ulcer recurrence. Significant patient morbidity may be prevented by using measures to eradicate H pylori during or after duodenal ulcer healing.

Amoxicillin

Solitary myeloma of the talus bone.

Solitary myeloma can present as either extramedullary plasmacytoma or solitary plasmacytoma of bone (SPB). More than half of reported cases of SPB are localized to the spine. The rest include appendage long bones of the skeleton, pelvis, and skull. The first case of SPB (to the authors' knowledge) is reported involving the talus bone of the foot. Although approximately 50% of SPB patients progress to multiple myeloma in the first 3 years after diagnosis, aggressive local therapy is indicated because the median survival of patients with SPB is better than that for multiple myeloma.

Bone Neoplasms

Recent clinical experience with dronabinol.

Dronabinol, delta-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

Antineoplastic Agents