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Biomedical subjects

B Yee

Publications and source records attributed to B Yee.

At least 19 recordsLinked to original sources

Sleep disorders: a potential role in New Zealand motor vehicle accidents.

BACKGROUND: The potential role of sleep disorders in New Zealand motor vehicle accidents (MVA) has not been systematically studied. AIMS: To trial a recruitment method and document the frequency of sleep disorders in drivers attending an emergency department with injury following MVA. METHODS: Injured drivers admitted to Wellington Hospital Emergency Department were prospectively recruited by letter and follow-up telephone call. Data from a traffic accident, health and sleep questionnaire and polysomnography were collected and analysed using the SPSS statistical package. RESULTS: Of 120 eligible drivers, 40 (33%) completed the study protocol. The mean age of participants was 44 +/- 17 years. Non-participants were younger (mean age 33 +/- 14 years, P < 0.01) and more often of Asian or Pacific Island ethnicity (P < 0.01). Twenty-seven (67%) felt unrefreshed on waking and 10 (25%) had an elevated Epworth Sleepiness Score (> 10/24). Six (15%) felt drowsy or fell asleep prior to the accident. Sleep disorders were common (40%): obstructive sleep apnoea 14 (35.9%), periodic limb movements of sleep three (7.7%), sleep restriction (< 6 h sleep on a regular basis) five (12.5%), and insomnia one (2.5%). CONCLUSIONS: Daytime somnolence and sleep disorders were commonly found in drivers attending the Emergency Department after accidents resulting in injury. Driver fatigue and sleep disorders should be considered as a potential contributing factor in New Zealand MVAs. Recruitment of drivers following a MVA via the Emergency Department is challenging. Strategies to improve recruitment are discussed.

Accidents, Traffic↗

Deafferentation of the hippocampus results in the induction of AT8 positive 'granules' in the rat.

Hyperphosphorylated tau is a pathological hallmark of Alzheimer's disease, but the mechanisms that lead to its formation are poorly understood. To investigate what effect deafferentation of the hippocampus has on the phosphorylation state of tau, we lesioned the entorhinal cortex in rats and looked for hyperphosphorylated tau in the hippocampus at various days post lesioning. After 7 and 21 days, small AT8-positive 'granules' appeared in the molecular layer of the dentate gyrus on the lesioned side. No such staining was seen in the animals injected with saline. This study shows that deafferentation leads to induction of hyperphosphorylated tau. The AT8 positive 'granules' seen resemble the argyrophilic grains that characterize Argyrophilic Grain disease suggesting that lesioning the perforant pathway may serve as a useful model for inducing argyrophilic grains in vivo.

Alzheimer Disease↗

Effects of female and male smoking on success rates of IVF and gamete intra-Fallopian transfer.

BACKGROUND: Smoking by both male and female partners may play a significant role in the success rates of assisted reproductive technologies. The objective of this 5-year prospective study was to investigate the influence of cigarette smoking by the wife, husband, and couple at various time points (e.g. lifetime, week prior, or during the procedures) on different biological parameters of IVF and gamete intra-Fallopian transfer (GIFT). METHODS AND RESULTS: A total of 221 couples, aged >20 years, of Caucasian, Black, Asian or Hispanic descent were recruited from seven infertility clinics located in Southern California. Couples (i.e. either female or male or both) who ever smoked compared with non-smokers, had adjusted relative risks (RR) of 2.41 (95% CI 1.07-5.45, P = 0.03) of not achieving a pregnancy, and 3.76 (95% CI 1.40-10.03, P < 0.01) of not having a live birth delivery, while adjusting for potential confounders. For couples who smoked for >5 years, there was an adjusted RR = 4.27 of not achieving a pregnancy (95% CI l.53-11.97, P = 0.01). The number of oocytes retrieved decreased by 40% for couples (smokers, n = 6) and by 46% for men who smoked during the week of the visit for IVF or GIFT. Women who smoked in their lifetime had adjusted risks of 2.71 of not achieving a pregnancy (95% CI 1.37-5.35, P < 0.01), and 2.51 (95% CI 1.11-5.67, P < 0.03) of not having a live birth delivery. CONCLUSIONS: There is compelling evidence that couples should be made aware that smoking years before undergoing IVF and GIFT can impact treatment outcome. This study may also provide insight into the timing and effects of male and female smoking on natural reproduction.

Adult↗

Agrin-induced acetylcholine receptor clustering is mediated by the small guanosine triphosphatases Rac and Cdc42.

During neuromuscular junction formation, agrin secreted from motor neurons causes muscle cell surface acetylcholine receptors (AChRs) to cluster at synaptic sites by mechanisms that are insufficiently understood. The Rho family of small guanosine triphosphatases (GTPases), including Rac and Cdc42, can mediate focal reorganization of the cell periphery in response to extracellular signals. Here, we investigated the role of Rac and Cdc42 in coupling agrin signaling to AChR clustering. We found that agrin causes marked muscle-specific activation of Rac and Cdc42 in differentiated myotubes, as detected by biochemical measurements. Moreover, this activation is crucial for AChR clustering, since the expression of dominant interfering mutants of either Rac or Cdc42 in myotubes blocks agrin-induced AChR clustering. In contrast, constitutively active Rac and Cdc42 mutants cause AChR to aggregate in the absence of agrin. By indicating that agrin-dependent activation of Rac and Cdc42 constitutes a critical step in the signaling pathway leading to AChR clustering, these findings suggest a novel role for these Rho-GTPases: the coupling of neuronal signaling to a key step in neuromuscular synaptogenesis.

Agrin↗

Comparisons of the densities of NADPHd reactive and nNOS immunopositive neurons in the hippocampus of three age groups of young nonhandled and handled rats.

The complete absence of handling of male rats during neonatal development (from birth to postnatal day 21) correlates with an impairment of latent inhibition [J. Feldon, I. Weiner, From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia, J. Psychiatr. Res. 26 (1992) 345-366.]. Such nonhandling of rats reportedly also correlates with a decreased expression of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reactivity in the hippocampus in adult rats (6 months of age) when compared with rats of the same age that were handled during the same neonatal period [R.R. Vaid, B.K. Yee, U. Shalev, J.N. Rawlins, I. Weiner, J. Feldon, S. Totterdell, Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn of rats, J. Neurosci. 17 (1997) 5599-5609.]. The present study investigated whether such a decrease in NADPHd activity would be detectable at earlier ages. Therefore, the present study assessed the density of nitric oxide (NO) producing neurons in the fascia dentata and Ammon's horn in 28-, 54-, and 118-day-old nonhandled and handled male rats using NADPHd histochemistry and immunohistochemical localization of neuronal isoform of nitric oxide synthase (nNOS), a NADPHd. This showed that in these three age groups, the numbers of NADPHd positive neurons per unit area throughout the hippocampus of rats that received no handling during neonatal development did not differ significantly from those of rats that received regular daily handling. In addition, we found in the rats of 118 days of age that the areal density of nNOS immunopositive neurons in the hippocampus also did not differ significantly between nonhandled and handled rats. Nevertheless, in a parallel study, rats from the same experimental group receiving identical treatments showed the expected impairment of latent inhibition at 4 months of age [R. Weizman, J. Lehmann, S. Leschiner, I. Allmann, T. Stoehr, C. Heidbreder, A. Domeney, J. Feldon, M. Gavish, Long-lasting effect of early handling on the peripheral-type benzodiazepine receptor, Pharmacol. Biochem. Behav. in press.]. These results suggest that nonhandling of rats during the early neonatal period, that does result in impairment in latent inhibition, does not affect the numbers of NO producing neurons in the hippocampus in rats of young ages, including the age of observed impairment of latent inhibition.

Aging↗

Improved human oocyte development after vitrification: a comparison of thawing methods.

OBJECTIVE: To evaluate the developmental competence of vitrified human oocytes thawed using two different methods to establish an effective cryopreservation protocol. DESIGN: In vitro model study. SETTING: University-affiliated hospital. PATIENT(S): Patients who underwent a long protocol of ovarian stimulation with GnRH and gonadotropins. INTERVENTION(S): Vitrified oocytes from the patients were thawed using either a four-step method with 2.5-minute intervals or a four-step method with 5-minute intervals. MAIN OUTCOME MEASURE(S): Morphologic normality, maturation, fertilization, and development of the oocytes to the blastocyst stage. RESULT(S): The two thawing methods did not significantly affect the morphologic normality (84%-100%), maturation (75%-100%), fertilization (38%-71%), polyspermy (more than three pronuclei; 0%-20%), or parthenogenetic activation (only female pronucleus; 0%-8%) of the vitrified oocytes. However, more of the vitrified oocytes developed to the two-cell (71%-100% versus 50%-67%), four-cell (71%-93% versus 0%-50%), eight-cell (46%-71% versus 0%), and blastocyst (23%-36% versus 0%) stages after thawing using the four-step method with 2.5-minute intervals than using the four-step method with 5-minute intervals. CONCLUSION(S): Vitrified human oocytes developed to the blastocyst stage with IVF. A four-step thawing method with 2.5-minute intervals was more effective in supporting preimplantation embryo development than a four-step thawing method with 5-minute intervals.

Adult↗

Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome.

Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS.

Actins↗

Assisted hatching reduces the age-related decline in IVF outcome in women younger than age 43 without increasing miscarriage or monozygotic twinning.

PURPOSE: Our purpose was to examine the benefits of assisted hatching in our program and to determine whether the procedure increases the implantation of nonviable embryos or monozygotic twinning. METHODS: Consecutive in vitro fertilization cycles using assisted hatching were compared with historical controls. The impact of assisted hatching was analyzed according to the woman's age. Outcome measures were clinical pregnancy, implantation rate, delivery rate, multiple pregnancy, spontaneous abortion, and incidence of monozygotic twins. RESULTS: The implantation rate was increased in women aged 35-39 and markedly increased in women aged 40-42. There was no change in spontaneous abortions and no increase in monozygotic twins. CONCLUSIONS: Assisted hatching is a safe and highly effective adjunct to in vitro fertilization for women aged 35-42 and did not increase spontaneous abortion or monozygotic twinning.

Abortion, Spontaneous↗

A simplified method of timing frozen embryo transfers.

OBJECTIVE: Our purpose was to compare a simple artificial hormone replacement regimen with two other protocols incorporating pituitary down-regulation with gonadotropin-releasing hormone agonist for frozen embryo transfers. STUDY DESIGN: We performed a retrospective analysis of pregnancy outcomes after 366 frozen embryo transfers timed by one of three hormone replacement regimens. The three regimens used were regimen A, leuprolide acetate and transdermal estradiol patches; regimen B, leuprolide acetate and oral micronized estradiol; regimen C, only oral micronized estradiol. RESULTS: The outcomes of 366 consecutive frozen embryo transfers according to one of the three regimens were compared and analyzed. The clinical pregnancy rates were 13.7%, 11.4% and 13.5% in regimens A, B and C, respectively. No statistical differences were found among the three regimens. The mean age of the patients in the three groups was comparable. The mean number of frozen embryos transferred with regimen B was slightly higher, but it did not have a positive impact on the pregnancy rate in this group. CONCLUSION: Controlled sequential hormone replacement results in an endometrium suitable for frozen embryo transfers. Pituitary down-regulation is not necessary. Therefore this regimen is not only more simple to use but also more economical.

Cryopreservation↗

Successful implantation of frozen sibling embryos is influenced by the outcome of the cycle from which they were derived.

OBJECTIVES: To determine if the success of frozen embryos obtained from assisted reproductive technology (ART) cycles is dependent upon the outcome of the ART cycle from which they were derived and to determine if the length of time in cryostorage affects pregnancy rates (PRs). DESIGN: Retrospective analysis of pregnancy outcome of consecutive frozen ETs compared with their corresponding "'fresh" cycles. SETTING: University-affiliated private ART program. PATIENTS: Between July 1986 and December 1992, 375 oocyte retrieval cycles had at least one subsequent frozen ET for comparison. Of the 375 patients, 94 achieved a clinical pregnancy during their fresh cycle (group A) and 281 patients did not (group B). INTERVENTIONS: Frozen ETs were performed using either natural (unstimulated) cycles (n = 79) or artificial cycles (n = 296). Transfers during natural cycles were timed with a combination of serum LH levels and ultrasound (US). These transfers were performed 2 days after ovulation. Ovarian suppression with leuprolide acetate followed by sequential estrogen and P replacement were used in the artificial cycles. These transfers were performed on the 3rd day of P administration. Clinical pregnancies were defined as the presence of a gestational sac on transvaginal US. MAIN OUTCOME MEASURES: Patients were compared based on the pregnancy outcome of their frozen ET cycle and fresh ART cycle. chi 2 analysis and Student's-tests were used to test for statistical significance. RESULTS: Twenty-three patients (24.1%) from group A achieved a pregnancy from their frozen transfers compared with only 24 patients (8.5%) in group B who achieved a pregnancy from their frozen cycle. PRs did not differ based on the method of follicle aspiration, laparoscopy versus transvaginal US retrieval. Significantly lower PRs were noted in frozen ETs done within the first 10 months after cryopreservation compared with fresh cycle PRs. CONCLUSIONS: Sibling embryos from a prior successful ART cycle are more likely to initiate a frozen pregnancy and prolonged cryostorage did not affect PRs. This higher PR probably reflects better quality in both fresh and frozen embryos. Therefore, the outcome of the initial cycle can be used to predict the success or failure of subsequent frozen transfers and oocyte-embryo quality appears to be key.

Adult↗

A 3,3'-diiodothyronine sulfate cross-reactive compound in serum from pregnant women.

Recently, we found high serum/urine concentrations of 3,3'-diiodothyronine sulfate (T2S) in both fetal and maternal sheep. In the present study, a RIA was employed to detect and measure serum T2S in women of different gestational ages and after delivery. Results were compared with values in nonpregnant women. In maternal serum, we identified a material that cross-reacts with T2S antibody, but is not T2S. Its concentration increased with the progression of pregnancy. The exact chemical structure of the T2S-like material (which we designated compound W) is unclear. It is immunologically (or chemically) similar to T2S, but does not cochromatograph with synthetic T2S in high pressure liquid chromatography. The serum concentrations of compound W were expressed as T2S equivalents (nanomoles per L +/- SE). Serum compound W concentrations were slightly elevated in women during the first trimester compared to those in nonpregnant women (0.73 +/- 0.04 vs. 0.17 +/- 0.02 nmol/L; P < 0.01). There was a moderate and progressive rise in the compound W concentration between 14-35 weeks gestation. The maternal serum compound W concentration then rapidly peaked before parturition (36-40 weeks gestation, 3.49 +/- 0.49 nmol/L; 27-35 weeks, 1.67 +/- 0.11 nmol/L; P < 0.01). After parturition, maternal serum levels of compound W decreased from 2.61 +/- 0.18 nmol/L (n = 25) to 1.47 +/- 0.12 nmol/L (n = 18) at 1 day, 0.89 +/- 0.07 nmol/L (n = 15) at 3 days, and 0.33 +/- 0.03 nmol/L (n = 8) at 7 days. hCG increased serum concentrations of T2S-cross-reactive material 6.2-fold (P < 0.01) in nonpregnant women. In summary, whereas hCG stimulation may account for some increase in maternal serum concentrations of this T2S-like material in the first trimester, the more rapid increase in maternal serum compound W concentrations during the late third trimester are probably related to changes that occur in fetal thyroid hormone economy. It is speculated that placental transfer and transformation of fetal T3 may be related to the rise in the level of T2S-like compound W in the serum of pregnant women.

Adolescent↗

The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity.

To evaluate the androgen control of sebum, subjects with complete androgen insensitivity and male pseudohermaphrodites with inherited 5 alpha-reductase deficiency and decreased dihydrotestosterone (DHT) production had sebum production studied. A hydrophobic polymeric film applied to the forehead was used to measure sebum production through the use of air filled micropores. Sebum scores of normal preadrenarchal children (ages 2-6), and normal age-matched adult males and females, were studied as well as males treated with the 5 alpha-reductase inhibitor, finasteride, for benign prostatic hyperplasia who were studied at baseline and after drug therapy. Androgen insensitive subjects had no sebum production by this methodology, and the results were identical to preadrenarchal children. In contrast, adult male pseudohermaphrodites with 5 alpha-reductase deficiency and a selective decrease in DHT production had sebum production scores identical to normal age-matched males. Males with benign prostatic hyperplasia treated with the 5 alpha-reductase inhibitor, finasteride, to lower DHT levels did not decrease the sebum score from baseline values. The lack of demonstrable sebum in androgen-insensitive subjects clearly demonstrates the absolute androgen control of sebum production. The DHT dependency of the sebaceous gland, however, could not be demonstrated in this study. Two 5 alpha-reductase isoenzymes 1 and 2, have been described. 5 alpha-reductase-2 is the gene responsible for inherited 5 alpha-reductase deficiency. Although the degree of inhibition of DHT in utero and in adulthood in male pseudohermaphrodites with a defect in 5 alpha-reductase-2 enzyme activity caused severe impairment of external genital and prostate differentiation and decreased facial and body hair, it had no demonstrable effect on sebaceous gland development or function. Furthermore, lowering DHT levels in adulthood had no effect on sebum production. If the gland is rich in the enzyme 5 alpha-reductase-2, it is proposed that the sebaceous gland is either exquisitely sensitive to DHT, requiring only small amounts for normal development and function, or that male levels of testosterone compensate for DHT and maintain normal sebaceous gland activity throughout life. It is also possible that 5 alpha-reductase-1 is the enzyme of the sebaceous gland and is unaffected in the inherited condition and by finasteride.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Ovulation induction in women with premature ovarian failure: a prospective, crossover study.

A prospective crossover study comparing ovulation induction techniques in eight women with premature ovarian failure is presented. These patients were treated with FSH rebound techniques using the GnRH-a, LA, alone in one treatment cycle and the same plus menopausal gonadotropins in the other treatment cycle. Two women ovulated in each group. We conclude that ovulation does occur in women with premature ovarian failure, but that luteal P may be inadequately secreted.

Adult↗

Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies.

Studies were performed to compare the effects of 5 alpha-reductase inhibition and antiandrogen receptor blockade on differentiation of male internal and external genital structures and prostate in the rat. Dose-response studies were performed on male rats treated in utero during the period of sexual differentiation with either the potent 5 alpha-reductase inhibitor finasteride or the antiandrogen flutamide. The treated animals were raised to adulthood and killed, and genital structures were evaluated. Treatment with the 5 alpha-reductase inhibitor finasteride at a dose of 25 mg/kg.day resulted in significant feminization of the external genitalia. There was no further feminization of the genitalia at doses up to 300 mg/kg.day. Wolffian ductal differentiation occurred at all doses evaluated. Seminal vesicle weight, however, significantly decreased at 25 mg/kg.day, but without a further decrease at higher doses of the 5 alpha-reductase inhibitor. Vas deferens and epididymal weights were unchanged at all doses evaluated. There was a significant decrease in prostate size at 25 and 50 mg/kg.day, with no further decrease at higher doses. In flutamide-treated animals, complete feminization of the genitalia occurred at 24 mg/kg.day in all animals. At 18 mg/kg.day, Wolffian ductal differentiation occurred, but seminal vesicle weight was decreased. At dosages of 100, 200, and 300 mg/kg.day flutamide, the vas deferens was absent unilaterally or bilaterally, with small remnants of epididymal head and tail present. At dosages of 24 mg/kg.day and above, the prostate was absent. Studies with the 5 alpha-reductase inhibitor finasteride demonstrate the dependency of prostate and male external genital differentiation on dihydrotestosterone (DHT). However, unlike androgen receptor blockade with flutamide, finasteride did not totally abolish prostate differentiation or completely feminize the external genitalia, despite increasingly higher doses. Since there is no evidence of multiple 5 alpha-reductase isoenzymes to date in the rat, these results suggest that testosterone (T) can compensate for DHT to some degree at the level of the androgen receptor. Wolffian differentiation, however, was not affected by inhibition of DHT, demonstrating its T dependency, but seminal vesicle growth was impaired. Thus, inhibition of 5 alpha-reductase activity limits seminal growth potential in adulthood. Studies with the antiandrogen flutamide show that at doses significantly above that required to completely block prostate differentiation and cause genital feminization, Wolffian ductal differentiation is significantly impaired. Thus, higher doses of flutamide are needed to block the paracrine effect of T on the Wolffian ducts.

5-alpha Reductase Inhibitors↗

Pulmonary paragonimiasis in Southeast Asians living in the central San Joaquin Valley.

We describe four cases of pulmonary paragonimiasis in Southeast Asians who emigrated to the central San Joaquin Valley of California. Physicians should be alerted to the possibility of this disease in Asian patients with hemoptysis and pulmonary infiltrates. Paragonimiasis can masquerade as pulmonary tuberculosis, especially in patients from areas that are endemic for both the parasite and the tubercle bacillus. The ease and safety with which this infection can be treated, in contrast to tuberculosis, reiterates the importance of diagnosing this lung fluke when it is present.

Adolescent↗

Predicting pregnancy outcome by the observation of a gestational sac or of early fetal cardiac motion with transvaginal ultrasonography.

Transvaginal ultrasound (US) allows for observation of the gestational sac and cardiac motion as early as 3 and 4 weeks after ovulation, respectively. The purpose of this study was to determine how well the first observation of cardiac motion, using weekly transvaginal US examinations, predicted pregnancy outcome. Three hundred sixteen pregnancies wherein the date of ovulation was known and a single gestational sac was visualized at 3 weeks after ovulation were studied. Cardiac motion was first detected at 4 weeks after ovulation in 226 (71.5%), and at 5 weeks in 67 (21.2%). In 23 patients, cardiac motion was never observed. In those patients with cardiac motion visible at 4 weeks after ovulation, 94.2% have subsequently delivered viable infants. This contrasts with only 70.1% for those patients who first had observable cardiac motion 1 week later (P = 6.7 X 10(-6]. This study demonstrates that the solo finding of a gestational sac is a poor predictor of pregnancy outcome (82.3% accurate) and that the earlier that cardiac motion is initially observed, the better the pregnancy prognosis.

Abortion, Spontaneous↗

Bilateral congenital absence of the fibula.

The syndrome caused by congenital absence of the fibula has a number of pathologic abnormalities frequently associated with it, which are illustrated by the case reported. Postsurgical therapy on the involved extremity should take into account the patient's lack of joint motion within the tarsal region. With this in mind, special shoes or accommodative insoles, alone or in combination, should be prescribed in order to facilitate an increase in weightbearing activity with minimal discomfort.

Abnormalities, Multiple↗