1/15. Impaired mitochondrial pyruvate importation in a patient and a fetus at risk.The patient was the first child of healthy consanguineous parents. She presented at birth with hypotonia, mild facial dysmorphism, periventricular cysts, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate molar ratios, normoglycemia, and normal ammonia. Hyperlactacidemia was severe (5-14 mmol/l) and not corrected with bicarbonate, thiamine (10 mg/d), 2-chloropropionate (100 mg/kg/d) and a ketogenic diet. Pyruvate dehydrogenase (PDHC) activity was normal in lymphocytes and fibroblasts. Functional assays were performed in digitonin-permeabilized fibroblasts to measure oxidation rates from radiolabeled pyruvate and malate. The production of [14C]acetylcarnitine or [14C]citric cycle intermediates derived from [2-14C]pyruvate as well as the release of 14CO(2) from [1-14C]pyruvate was severely impaired, whereas decarboxylation of [U-14C]malate was normal. With increasing concentrations of [1-14C]pyruvate, the patient's fibroblasts behave like control fibroblasts incubated in the presence of alpha-cyano-4-hydroxycinnamate, a specific inhibitor of mitochondrial pyruvate uptake: a progressive increase in 14CO(2) production was observed, likely due to passive diffusion of [1-14C]pyruvate through the mitochondrial membranes. Our results are consistent with a defect of mitochondrial pyruvate transport in the patient. Mutational analysis was precluded as the cDNA sequence of the pyruvate carrier has not been identified as yet in any organism. An affected fetus was recognized in a subsequent dichorionic twin pregnancy using the coupled assay measuring [2-14C]pyruvate oxidation rates on digitonin-permeabilized trophoblasts. After selective feticide, the pregnancy was uncomplicated with delivery at 37w of a healthy female, who is currently 2-month old.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/15. Concordant rhabdoid tumor of the kidney in a set of identical twins with discordant outcomes.We report identical twin boys who each had stage IV rhabdoid tumor of the left kidney at the age of 5 months and 2 years, respectively. The 5-month-old boy, despite receiving chemotherapy, died of progressive disease at the age of 12 months. Following resection of the tumor, his twin brother was treated with 6 cycles of combination chemotherapy consisting of cisplatinum, doxorubicin, vincristine, cyclophosphamide, and actinomycin-D alternating with ifosfamide and etoposide. After complete regression of lung and brain metastases, he received high-dose thiotepa, etoposide, and cyclophosphamide, followed by autologous peripheral stem cell rescue. The patient is presently alive and free of disease 6 years posttransplant. High-dose chemotherapy followed by autologous stem cell transplant may be an effective front-line therapeutic approach for patients with metastatic rhabdoid tumor of the kidney.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
3/15. Severe, neonatal-onset OTC deficiency in twin sisters with a de novo balanced reciprocal translocation t(X;5)(p21.1;q11).OTC deficiency, the most common urea cycle defect, is transmitted as a partially dominant X-linked trait. The most severe form of the disease, however, is usually restricted to males. We report on monozygotic female twins with severe neonatal-onset OTC deficiency and a de novo balanced reciprocal translocation t(X;5)(p21.1;q11). Disruption of the OTC gene on the derivative X-chromosome was confirmed by FISH analysis. Consistent inactivation of the normal X could be demonstrated by RGB staining. Manifestation of X-linked recessive disorders in females due to a balanced reciprocal X-autosome translocation has previously been described in Duchenne muscular dystrophy and several other disorders but not in OTC deficiency. This report emphasizes the importance of chromosome analysis in any female manifesting severe OTC deficiency.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
4/15. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure.Monozygotic 24-year-old twins presented with discordant ovarian function. One had had premature ovarian failure at the age of 14 years, whereas her sister had normal ovaries and three naturally conceived children. After unsuccessful egg-donation therapy, the sterile twin received a transplant of ovarian cortical tissue from her sister by means of a minilaparotomy. Within three months after transplantation, the recipient's cycles resumed and serum gonadotropin levels fell to the normal range. During the second cycle, she conceived, and her pregnancy progressed uneventfully. At 38 weeks' gestation, she delivered a healthy-appearing female infant.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
5/15. Anesthetic management of patients with ornithine transcarbamylase deficiency.ornithine transcarbamylase deficiency (OTCD) is the most common inborn error of the urea cycle. Several specific factors require care during anesthesia in patients with this condition to avoid metabolic decompensation with acute hyperammonemia and encephalopathy. We report monozygous twins with severe neonatal-onset OTCD undergoing general anesthesia twice each, with midazolam, s-ketamine, fentanyl and isoflurane in combination with surgical field infiltration with ropivacaine. Alternative pathway medication and high-caloric diet with 10% glucose solutions were continuously administered during the perioperative course. Both children were extubated within 10 min of the final suture, and their neurological state remained unchanged. Perioperatively, blood ammonia levels remained within the normal range.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
6/15. Evidence for blood chimerism in dizygotic spontaneous twin pregnancy discordant for down syndrome.BACKGROUND: A monochorionic-diamniotic placenta (MCDAP) is rare in dizygotic (DZ) twinning. All reported cases have been documented in pregnancies achieved by the induction of ovulation alone or during the IVF cycle. methods AND RESULTS: We report a spontaneous pregnancy in a 39-year-old patient with evidence of MCDAP in DZ twins, discordant for trisomy 21. The first and second-trimester sonographic scans indicated male twins with MCDAP. amniocentesis, performed because of advanced maternal age, revealed a normal karyotype in one fetus, and trisomy 21 in the other. Molecular studies, performed in order to confirm the zygosity and chorionicity, demonstrated that the fetuses were DZ. In order to identity the affected twin, a detailed sonographic examination was repeated, but no abnormal findings associated with down syndrome were demonstrated in any of the fetuses. Therefore, umbilical cord blood samples were obtained from both fetuses. Chromosomal analysis revealed in both fetuses two cell lines: a normal cell line of 46,XY and a 47,XY, 21 cell line, in 65 and 80% of the cells, respectively. This result was independently confirmed by both FISH and G-banding. dna extracted from both cord blood samples demonstrated an admixture of two distinct genotypes in each sample. CONCLUSIONS: We propose that this case represents a monochorionic-dizygotic twin pregnancy with blood chimerism. The most plausible mechanism underlying this phenomenon is placental fusion early in pregnancy, resulting in an architecturally single placenta originating from two distinct zygotes. The newly formed blood vessels created anastomoses between the DZ twins and allowed reciprocal blood chimerism between the normal and the trisomic twin.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
7/15. Cyclic neutropenia in identical twins.Cyclic neutropenia developed in identical twin girls. The onset of neutropenia in these children occurred three years apart. Neutrophil cycling diminished, and symptoms decreased in the initially affected twin during a five-year follow-up. Some cases of cyclic neutropenia may be genetically determined; however, the onset and clinical manifestations may be modified by other internal and external factors. There may also be a prodromal period during which neutrophils cycle, but the patient is neither neutropenic nor symptomatic.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
8/15. Psychophysiologic circadian rhythmometry on manic-depressive twins.Rhythmometry on emotionally disturbed identical twins is applied for study of possible emotional chronopathology. Several circadian rhythmic variables are apparently 24-h synchronized in both twins, during a study span associated with mania in one twin and apparently 'normal' behavior in the other. While the data span of 3 weeks does not allow validation of any desynchronization with a period quite near to 24 h in the case of a manic girl, it does not rule out the possibility of uncoupling of an adrenal cortical cycle, gauged by the circadian rhythm in urinary 17-ketosteroid excretion. The question whether circadian or other dyschronism was present, and, if so, represented a trivial corollary or, perhaps, a determinant of emotional pathology, remains unanswered. The methodology here illustrated and added tests of differences in rhythm characteristics are likely to provide answers to such questions when they are combined with therapeutic manipulations and the search for possible chronobiotic drugs.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
9/15. Cyclic neutropenia and T lymphocyte suppression of granulopoiesis: abrogation of the neutropenic cycles by lithium carbonate.To investigate the mechanisms of cyclic neutropenia, we studied the capacity of a patient's T lymphocytes (TLp) to interact with monocyte-macrophages from her normal HLA-identical sibling (MOb) in the elaboration of colony-stimulating activity (CSA). TLp obtained at the time of decreasing neutrophil counts, increased CSA elaboration (p less than 0.056) when incubated at a 1:1 ratio with MOb. Increasing the TLp to MOb ratios to 3:1 or 5:1 progressively decreased CSA. Also, lithium carbonate, which ordinarily prevents concanavalin a activation of suppressor TL, failed to do so, suggesting that preactivated suppressor TL were present in the patient while neutrophil levels were falling. In similar experiments performed while neutrophil levels were rising these activated suppressor TL were absent. These data suggest that some patients with cyclic neutropenia may have a cyclic increase in suppressor TL activity. As predicted by our in vitro experiments, lithium carbonate administration did not abrogate the first neutropenic cycle, but it did mitigate subsequent cycles.- - - - - - - - - - ranking = 6keywords = cycle (Clic here for more details about this article) |
10/15. Pericentric X inversion in dizygotic twins who differ in x chromosome inactivation and menstrual cycle function.A 21-year-old female dizygotic twin was referred for cytogenetic evaluation because of mild mental retardation. Significant history, clinical, and physical findings included irregular menses, mildly coarse facies, and microcornea. Chromosome analysis revealed a pericentric inversion of the X chromosome, 46, X, inv (X)(p11;q22). Her twin who is phenotypically normal was also found to carry the same inversion. The twins differ significantly in x chromosome inactivation and menstrual cycle function.- - - - - - - - - - ranking = 5keywords = cycle (Clic here for more details about this article) |
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