Biomedical subjects
Publications and source records attributed to C Chau.
We present a case of simultaneous abdominal and intrauterine pregnancy following in vitro fertilization and embryo transfer diagnosed during the second trimester. The patient had a recent history of hysteroscopic metroplasty due to in utero exposition to diethylstilboestrol. The pregnancy was managed conservatively with a favorable outcome for the mother and both fetuses.
While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.
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It is known that maternal immunological factors such as systemic disease are involved in the genesis of cardiac conduction problems in the fetus but the histologic changes in the conduction system are less documented. We report the case of a 33-year-old woman with no significant medical history. Her first pregnancy was induced by Clomifene. At 17 weeks of gestation, the fetus presented sonographic abnormalities characteristic of a complete atrioventricular block. Biological investigations found anti-SSA and -SSB antibodies. Clinical history search for systemic disease was positive for photosensitivity, lasting 10 years, suggesting the diagnosis of systemic lupus erythematosus. The patient was treated with prednisone 20 mg per day but fetal death occurred at 29 weeks of gestation. Histological examination of the fetal heart showed an altered atrioventricular node and bundle of His with fibrosis, calcifications, endocardial fibroelastosis and mononucleated inflammatory cells. The search for these specific lesions can be determinant in establishing the disease pathogenesis; also, it is important to eliminate this diagnosis in an unexplained fetal death.
We report ICSI pregnancies in two couples with a history of long standing primary infertility in which the sperm of the male partner were either acephalic or had abnormal head-midpiece attachments. The two couples, in which the men are brothers, underwent ICSI. Sperm were analysed by transmission electron microscopy and immunocytochemistry with an anti-MPM2 monoclonal antibody. The first couple underwent two ICSI cycles, each consisting of the injection of two mature oocytes and the transfer of two embryos. A successful pregnancy occurred after the second transfer and led to the birth to a healthy girl. The second couple underwent three ICSI cycles, each consisting of the injection of 18 oocytes and the transfer of two embryos; the last of these led to a triple ongoing pregnancy which included two identical twins. Caesarean section led to the birth of three fetal-growth restricted children. This case report demonstrates that ongoing pregnancies can be achieved in cases of abnormal development of the head-neck attachment. The genetic origin of this syndrome is generally accepted, but the phenotypic heterogeneity observed by light and electron microscopy among published cases suggests that there are a variety of genetic causes of this syndrome.
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OBJECTIVE: To evaluate the usefulness of transvaginal ultrasonography in the determination of the risk of preterm delivery and chorioamnionitis in pregnancies affected by preterm premature rupture of membranes preterm premature rupture of membranes. DESIGN: One hundred and one singleton pregnancies with preterm premature rupture of membranes were included in this prospective study over a 3-year period. Patients underwent cervical length measurement by transvaginal ultrasonography at admission and thereafter, in the absence of chorioamnionitis, were managed expectantly. RESULTS: The median time interval between admission and delivery (latency period) was 48 h. A cervical length of less than 20 mm was associated with a significant risk of early delivery (mean latency period was 59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation between cervical length and occurrence of chorioamnionitis or neonatal sepsis. CONCLUSIONS: These data suggest that the use of transvaginal ultrasonography for cervical length measurement during preterm premature rupture of membranes may predict an early delivery but cannot anticipate the risk of chorioamnionitis or neonatal sepsis.
This Topical Review summarizes some of the work we have done mainly in the cat using agonists and antagonists of various neurotransmitter systems injected intravenously or intrathecally to initiate or modulate the expression of hindlimb locomotion after a spinal lesion at T13. The effects of the same drugs are compared in various preparations: complete spinal, partial spinal or intact cats. This has revealed that there can be major differences in these effects. In turn, this suggests that although the locomotor rhythm might normally be triggered and modulated by the activation of a variety of receptors (noradrenaline, serotonin, glutamate), after spinalization there appears to be a predominance of glutamatergic mechanisms. Recent work also suggests that, in the cat, the integrity of the midlumbar segments is crucial for the expression of spinal locomotion. Taken together, this work raises some hope that a targeted pharmacotherapy with better understood drugs and mode and locus of delivery could become a clinical reality.
Verrucous carcinoma (VC), a variant of squamous cell carcinoma (SCC), is distinct from SCC in morphology and behavior. The underlying genetic changes involved in the development of VC and its precursor verrucous hyperplasia (VH) are unknown. This study determined whether chromosomal regions frequently lost during the development of SCC are also lost in the VH/VC variant. Twenty-five VH and 17 VC were analyzed for loss of heterozygosity (LOH) at 19 loci on 7 chromosome arms using microsatellite analysis. These data were compared with those from 47 reactive hyperplasias, 92 dysplasias (54 low- and 38 high-grade), and 41 SCCS: The results showed that VC/VH shared many of the losses present in dysplasia/SCC but differed in two aspects. First, VC/VH showed early acquisition of loss, compared with a gradual accumulation of losses from dysplasias to SCC. The LOH pattern of VH was similar to that of high-grade dysplasia and sharply different from reactive hyperplasia. The loss in VH often involved multiple arms (in 60% of VH vs 0% of reactive lesions). Only a marginal elevation of loss was observed at 9p (p = 0.06) and 4q (p = 0.05) from VH to VC because of the high degree of loss already present in VH. Second, a strikingly lower frequency of loss at 17p was noted in VH/VC compared with dysplasia/SCC and may indicate human papillomavirus (HPV) involvement. The finding of high-risk LOH profiles in VH may partly account for the high-progression risk seen for VH and also has potentially important clinical implications. The difficult pathological diagnosis of VH/VC from reactive hyperplasia frequently requires repeated biopsies and results in delay in diagnosis and significantly increased mortality/morbidity. Microsatellite analysis might facilitate this differential diagnosis.
We describe the presence of functional GABA(A) receptors on T cells. GABA inhibited anti-CD3 and antigen-specific T cell proliferation in vitro in a dose-dependent manner that was 1) mimicked by the GABA(A) receptor agonist muscimol (but not the GABA(B) receptor agonist baclofen), 2) blocked by GABA(A) receptor antagonists and a GABA(A) receptor Cl- channel blocker (picrotoxin) and 3) enhanced by pentobarbital. These data suggest that GABA(A) receptors mediate this immune inhibition and that these receptors can be modulated in a similar fashion to their neuronal counterparts. Finally, GABA inhibited DTH responses in vivo. Thus, pharmacological modulation of GABA(A) receptors may provide new approaches to modulate T cell responses in inflammation and autoimmune disease.
This short-term longitudinal study examined the associations between peer reports of victimization and self-reported friendship among early adolescents. It was carried out to test the view that friendship provides protection against victimization (called the "friendship protection hypothesis"). Data were collected at two points within a school year, separated by 6 months. At Time 1, 170 pupils provided data, and 158 of these did so again at Time 2. Three sets of findings were consistent with the friendship protection hypothesis. First, at Time 1 those early adolescents who had a reciprocated best friend in their home class received significantly fewer peer nominations for victimization than did classmates without a reciprocated best friend. Second, those early adolescents that did not have best friend at either Time 1 or Time 2 showed the highest increase in victimization over the course of the study, whereas those that did have a best friend at both Times 1 and 2 showed the highest falls in victimization. Third, a hierarchical multiple regression analysis indicated that a decrease in conflict and betrayal reported to characterize the participants' best friendship was associated with falls in victimization. The implications of these results for anti-bullying initiatives based on "befriending" principles were discussed.
Pharmacological agents have been shown to be capable of inducing a pattern of rhythmic activity recorded in muscle nerves or motoneurons of paralyzed spinal cats that closely resembles the locomotor pattern seen in intact cats. Further work, using intraperitoneal or intrathecal injections, suggests that different neurotransmitters may be involved in various aspects of locomotor control, e.g., initiation and modulation of the pattern. Although precursors, agonists or the neurotransmitters themselves of several systems have been investigated (noradrenergic, dopaminergic, serotonergic, glutamatergic), the noradrenergic system seems the most efficient in triggering locomotion in complete spinal cats, with the alpha-2 agonists (clonidine, tizanidine, oxymetazoline) being more potent than the alpha-1 agonist, methoxamine. Moreover, the potency of the drugs may depend on the time of application after the spinal lesion. In chronic spinal cats capable of spontaneous walking on hindlimbs on the treadmill, all neurotransmitters appear to exert distinct recognizable effects on the locomotor pattern. More recent work also suggests that the effects of drugs may differ significantly depending on the type of spinal lesion. For instance, clonidine further reduces the level of weight support during quadrupedal locomotion of cats with lesions of the ventral-ventrolateral funiculi, possibly due to an interference of clonidine with essential compensatory mechanisms used by these animals to walk. Such considerations as the type of drugs, type of lesions, and the time after the lesion will be important for future studies in spinal cord injured patients.
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Little is known about the immunological impact of insulin administration other than it can boost insulin autoantibody levels. In particular, while the subcutaneous administration of a soluble foreign antigen (without adjuvant) is generally only weakly immunogenic in a naive animal, it is unknown what effect the subcutaneous administration of a soluble self-antigen has in animals with established autoimmune responses to the antigen. Addressing these questions in pre-diabetic nonobese diabetic (NOD) mice, we examined the effects of administering insulin, as well as the metabolically inactive B-chain of insulin, on insulin-specific cellular and humoral immune responses. We show that pre-diabetic NOD mice have a spontaneous Th1-biased response against insulin. Administering insulin, or the insulin B-chain, rather than boosting the established Th1 response, primed Th2 cellular and humoral immunity to insulin, shifting the predominant insulin response toward a Th2 phenotype. Despite the presence of a Th1 response against insulin, insulin treated mice failed to mount proliferative T-cell responses following immunization and challenge with insulin, demonstrating that the treatment induced an active form of tolerance to this autoantigen. Thus, the subcutaneous administration of a soluble antigen can engage Th2 responses and induce self-tolerance, even after the establishment of autoreactive Th-1 responses. Such immune deviation and induced regulatory tolerance may contribute to the protective effects of prophylactic insulin therapy, as well as the establishment of a "honeymoon" phase in new-onset insulin-dependent diabetic patients.
Clonidine, a noradrenergic alpha-2 agonist, can initiate locomotion early after spinalization in cats. Because this effect lasts 4-6 h, we have injected clonidine daily, intraperitoneally or intrathecally, and intensively trained five spinal cats to perform hindlimb walking on a treadmill starting at day 3 and continuing until 10 days posttransection. Each day, clonidine was injected to induce locomotor activity and cats were trained to walk with as much weight support as possible and at different speeds during multiple (1-5) locomotor training sessions, each lasting from 10 to 20 min, until the effects of clonidine wore off. Electromyographic (EMG) activity synchronized to video images of the hindlimbs were recorded before and after each clonidine injection. The results showed, first, a day-to-day change of the locomotor pattern induced by clonidine from the 3rd to the 11th day including an increase in the duration of the step cycle, an increase in the duration of extensor EMG activity, and an increase in total angular excursion of the hip, knee, and ankle joints. Second, after 6-11 days of this regimen, there was an emergence of a coordinated locomotor pattern with weight support of the hindquarters that was visible even before that day's clonidine injection. The results suggested that daily injection of clonidine followed by early and daily interactive locomotor training can enhance the recovery of locomotion in spinal cats.
Noradrenergic drugs, acting on alpha adrenoceptors, have been found to play an important role in the initiation and modulation of locomotor pattern in adult cats after spinal cord transection. There are at least two subtypes of alpha adrenoceptors, alpha1 and alpha2 adrenoceptors. The aim of this study was to investigate the effects of selective alpha1 and alpha2 agonists in the initiation and modulation of locomotion in adult chronic cats in the early and late stages after complete transection at T13. Five cats, chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used in this study. Noradrenergic drugs including alpha2 agonists (clonidine, tizanidine, and oxymetazoline) and an antagonist, yohimbine, one alpha1 agonist (methoxamine), and a blocker, prazosin, as well as norepinephrine were injected intrathecally. EMG activity synchronized to video images of the hindlimbs were recorded before and after each drug injection. The results show differential effects of alpha1 and alpha2 agonists in the initiation of locomotion in early spinal cats (i.e., in the first week or so when there is no spontaneous locomotion) and in the modulation of locomotion and cutaneous reflexes in the late-spinal cats (i.e., when cats have recovered spontaneous locomotion). In early spinal cats, all three alpha2 agonists were found to initiate locomotion, although their action had a different time course. The alpha1 agonist methoxamine induced bouts of nice locomotor activity in three spinal cats some hours after injection but only induced sustained locomotion in one cat in which the effects were blocked by the alpha1 antagonist prazosin. In late spinal cats, although alpha2 agonists markedly increased the cycle duration and flexor muscle burst duration and decreased the weight support or extensor activity (effects blocked by an alpha2 antagonist, yohimbine), alpha1 agonist increased the weight support and primarily the extensor activity of the hindlimbs without markedly changing the timing of the step cycle. Although alpha2 agonists, especially clonidine, markedly reduced the cutaneous excitability and augmented the foot drag, the alpha1 agonist was found to increase the cutaneous reflex excitability. This is in line with previously reported differential effects of activation of the two receptors on motoneuron excitability and reflex transmission. Noradrenaline, the neurotransmitter itself, increased the cycle duration and at the same time retained the cutaneous excitability, thus exerting both alpha1 and alpha2 effects. This work therefore suggests that different subclasses of noradrenergic drugs could be used to more specifically target aspects of locomotor deficits in patients after spinal injury or diseases.
We report on a case of fetal goitrous diagnosed on ultrasonogram done at 31 weeks of gestation. Thyroid maternal function was normal and no therapeutic was responsible. Hormonal test done on cord blood supported diagnosis of prenatal hypothyroidism. The infant was born prematurely at gestation age of 34 without antenatal treatment. He was eutrophic with clinical and biological signs of hypothyroidism and a large goiter. Therapy with thyroxine was instituted on the third day of life. At 9 months, growth and development are normal. Congenital hypothyroidism has an incidence of approximately 1 in every 4000-5000 live births. Rarely fetal goitrous hypothyroidism have been attributed to thyroid hormone dyshormonogenesis. When fetal goiter is diagnosed on ultrasonography, without maternal hypothyroidism or therapeutic and when hypothyroidism is confirmed on fetal blood, this diagnosis must be suspected.
Our purpose was to evaluate fibronectin as a marker of endothelial cell injury, and as a test for predicting preeclampsia. A retrospective study was performed from November 1993 to March 1995. Results from 142 women were examined: 108 normal pregnant women and 34 pregnant women with evidence of preeclampsia. The plasma fibronectin concentration was significantly higher in pre-eclamptic gravidas (620 +/- 210 mg/l) than in normotensive gravidae women (390 +/- 130 mg/l). A fibronectin concentration lower than 400 mg/l predicted the non-development of a hypertension with a negative predictive value of 96%. The present findings suggest that fibronectin is rather an exclusion parameter than predictive test for hypertension disorders of pregnancy.