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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 1,153 records · Page 64Linked to original sources

[Timing of embryo transfer and success of pregnancy in the human].

The best moment for human embryo transfer has not yet been accurately determined. The human uterus is able to receive young embryos (2, 4 cell-stage and even pronucleated eggs), insure their growth and implantation at a rate that does not exceed, however, 15% for one transferred egg. At the present time in vitro culture to the blastocyst stage, which impairs human embryo viability, should be avoided. Contrary to classical IVF, it becomes possible to dissociate embryo and endometrial ages when transferring frozen-thawed eggs. Our study concerns 443 spontaneous, stimulated or artificial cycles, performed in patients with normal or without endogenous ovarian function (tabl. 1). There was trend towards enhanced pregnancy rates (17%) for synchronous as compared to one-day asynchronous transfers (9%) (tabl. 2). Similar data, widely stated in mammals, emphasize the necessity of a precise chronology of embryo transfer. Embryos only survive and get implanted when placed in a receptive uterus. The onset of the refractory period appears to be closely linked to the maternal steroid environment. Consequently, no pregnancies arose from transfer of donated embryos beyond 6 days of progestative supply in women deprived of endogenous ovarian function. In the same way, administration of progesterone 40 h before oocyte recovery seemed to advance the refractory phase. Indeed, a reduction in the pregnancy rate per transfer was observed in such circumstances without any obvious impairment of embryo viability (tabl. 4). The best pregnancy rate was obtained in synchronous transfers while a one-day disynchronization reduced this rate by half.

Animals↗

[Failure of embryonic development].

Abnormal embryo development represents the major cause of implantation failures and accounts for the low rate of human fertility in vivo or in vitro. Chromosome abnormalities are widely involved in this process as 26% of oocytes, 8% of fertilizing spermatozoa and 29% of preimplantation embryos carry a chromosome aberration induced by meiotic (aneuploidy) or mitotic (mosaic) non disjunctions. Fertilization anomalies (possibly increased by in vitro procedures) were recorded: 1.6% of embryos resulted from parthenogenesis and 6.4% were polyploid (mainly polyspermic). A morphological, histological and ultrastructural study of embryos recovered after in vivo or in vitro fertilization showed some anomalies: multinucleated blastomeres, cytoplasmic fragments in the perivitelline space, vacuoles, associated or not with developmental impairement. Finally, a few embryos appeared to be free of abnormalities. The analysis of in vitro developmental capacities of normal or abnormal embryos showed great differences: parthenones exceptionally reached the blastocyst stage and therefore probably did not implant. The diploid embryos used in this study were (for ethical reasons) more or less fragmented and gave evidence of low developmental capacities, limited to the 3rd cleavage. Triploid embryos were able to further develop as some of them reached the early blastocyst stage; they represented the major cause of chromosomal 1st trimester abortions. It is interesting to note that 47% of tripronucleated ova divided directly into 3 and 6 cells (probably via a tripolar spindle) instead of 2 and 4 cells as classically described. Finally, tetraploid embryos expressed a precocious lethality as none developed beyond the 3rd cleavage. To conclude, many embryos carry genetic and/or cytological abnormalities which may be enhanced by superovulation treatments. The selection proceeds through all pre- and postimplantation steps, and as a matter of fact nor more than 0.6% newborns are abnormal.

Chromosome Aberrations↗

Financial risk and hospital cost for elderly patients in non-age stratified surgical DRGS.

Hospitals face increasing uncertainty under prospective payment systems such as Medicare's DRG system. We analyzed the equity of the DRG system for 2622 Medicare surgical patients in the 82 non-age stratified surgical DRGs. Patients age 70 and over had higher total hospital costs (P less than .05), a longer hospital length of stay, more diagnoses per patient, losses under DRG payment (P less than .01), a greater percentage of outliers (P less than .05) and higher mortality than patients in these same DRGs under 70 years of age. This data suggests that the current DRG classification scheme may be inequitable vis-a-vis older Medicare patients in the non-age stratified surgical DRGs, and could provide financial disincentives that limit both their access and quality of care in the future.

Age Factors↗

[Chromosome analysis of ovocytes and human embryos collected after fertilization in vitro. A model of natural selection against aneuploidy].

Fertilization in-vitro offers the possibility of studying the karyotype of ovocytes obtained after superovulation, when they are not fertilized. Among 120 ovocytes, 30 p. cent presented a chromosomal anomaly. The same study was carried out on morphologically normal or abnormal embryos - and the percentage of chromosomal anomalies approximates here 27 p. cent. These studies offer a model of natural selection against chromosomal anomalies and confirm the limiting role of these anomalies in the success of FIV.

Aneuploidy↗

Observations on the role of endotoxin in graft-versus-host disease.

We have used a conventional murine model of bone marrow transplantation (BMT) to make a detailed study of the histological features of graft-versus-host disease (GvHD), and to study the effects of oral antibiotic decontamination of the gut flora. Comparison of the histological appearances of the small and large bowel indicated that the features of the GvHD were more severe in the large bowel. Bowel sterilisation caused a striking reduction in the severity of GvHD, both in the gut and at a distant site (the skin of the ear). The different effects of GvHD in the large as compared to the small bowel suggested that a factor was operative locally, and the effect of sterilisation linked this to the bacteria in the bowel. The fact that sites remote from the bowel were also affected suggested that a diffusible factor from the bowel produced by the bacteria of the gut was responsible. Studies elsewhere have suggested that the factor involved is likely to be endotoxin. In these experiments however it was evident that systemic administration of endotoxin did not aggravate the disease process and that in some instances the reverse was obtained. If therefore endotoxin is important the dose and its mode of its administration are likely to be critical.

Animals↗

[Fertilization in vitro today and tomorrow].

Today, it is possible to alter man's biological data, especially by acting on the procreation data. Progress in techniques permitting the development of assisted births (from artificial insemination to test-tube babies, from surrogate mothers to frozen embryos) and in techniques leading to procedures on the genetic make-up itself, is breathtaking. Through an analysis of the various advances in human procreation, the author wonders about the mutation we are experiencing and its impact on the future.

Attitude↗

Presurgical prediction of postsurgical visual acuity in patients with media opacities.

Of the estimated 1 million patients each year in the United States who undergo surgery for media opacities, perhaps 5-10% fail to improve because of pre-existing, undiagnosed retinal and/or optic nerve disease. In this paper, the standard presurgical evaluation (case history, visual acuity, refraction, pupillary response testing, biomicroscopy, ophthalmoscopy, tonometry, visual fields and color vision) and the supplementary presurgical evaluation (entoptic phenomena appreciation, ophthalmic ultrasonography, fluorescein angiography, laser interferometry, potential acuity meter, visual evoked potential, electroretinography, contrast sensitivity and hyperacuity measurements) are reviewed.

Cataract↗

Production of a positive direct antiglobulin test due to suramin.

Drugs and chemicals containing multiple reactive carbonyl groups have been postulated to produce nonimmunologic positive direct antiglobulin tests (DATs) both in vitro and in vivo. Suramin sodium, a reverse transcriptase inhibitor that was under investigation as a potential treatment for human immunodeficiency virus infection, has six reactive carbonyl groups. Because of suramin's chemical structure, it was hypothesized that the drug might cause a positive DAT in vitro and possibly in vivo. Suramin was found to produce a positive DAT in vitro at concentrations of 2100 mg/L or greater but did not cause a positive DAT in five patients with acquired immunodeficiency syndrome who were treated with suramin, probably because the serum levels of suramin were too low in these patients (peak therapeutic blood levels ranged from 171 to 443 mg/L).

Acquired Immunodeficiency Syndrome↗

Postnatal development of phenylethanolamine-N-methyltransferase activity of rat retina.

The postnatal development of rat retinal phenylethanolamine-N-methyltransferase (PNMT) activity was measured by radiometric assay. Activity was detected on day 1 of life. Retinal PNMT activity of day 1 neonates approximated 10% that of the adult. There is an increase in enzyme activity before eye opening. By day 30, enzyme activity has peaked. The enzyme during this early period possesses the same substrate specificity and inhibitor sensitivity as that of the adult enzyme. PNMT activity is detected before tyrosine hydroxylase activity.

Animals↗

[Autoimmune abortive disease. A new entity of gynaeco-obstetrical expression].

The relationship between abortive disease and systemic lupus erythematosus is complex as shown by data from the literature and by our 9 patients selected for presenting with abortive disease, circulating anticoagulant and biological signs of autoimmunity. The risk of transformation into a systemic disease is real, although difficult to evaluate in the absence of prospective studies, but the major problem with these patients is the severity of the obstetrical pathology. The sombre foetal prognosis, already reported in the literature, requires close supervision and sustained treatment during pregnancy. For these reasons we suggest calling autoimmune abortive disease the disease which affects women with signs of autoimmunity who have had several, often late foetal deaths associated with the presence of circulatory anticoagulant thought to interfere with placental blood flow.

Abortion, Habitual↗

Highly potent and specific inhibitors of human renin.

We have designed and synthesized a series of small peptides containing a perfluoroalkyl ketone group at the C-terminal position of the angiotensin I sequence as inhibitors of human renin. From this series of compounds, 8 and 10 showed strong inhibition of human renin (IC50 = 3 X 10(-9), 7 X 10(-9) M, respectively). Compound 10 did not inhibit pepsin and cathepsin D at 10(-4) M. Comparison of the IC50 of compound 8 and compound 11 (8.7 X 10(-7) M) demonstrated the marked effect of the perfluoropropyl group on the potency of inhibition on renin, presumably due to the strong electron-withdrawing effect causing the ketone in 8 to exist predominantly as the hydrate--thus mimicking the tetrahedral transition state during hydrolysis of the scissile Leu10--Val11 amide bond.

Cathepsin D↗

An enzyme-linked immunosorbent assay using adsorbed mycobacterial sonicates for the serodiagnosis of tuberculosis.

Sera from 123 patients with confirmed tuberculosis and 576 patients with other non-mycobacterial diseases were tested for antibodies to an adsorbed mycobacterial sonicate antigen employing an enzyme-linked immunosorbent assay. The results show significant differences in IgG levels between sera from tuberculosis patients and controls. The results of delayed hypersensitivity skin-test reactions to purified protein derivative in both the patient and control groups were unrelated to antibody levels. The assay was able to detect antibodies for at least 4 months after diagnosis and treatment. Patients diagnosed as having tuberculosis 7 months or more before being tested did not demonstrate increased antibody levels. The assay could be useful not only as a screening technique for diagnosing tuberculosis in an immunised population but also as a means of monitoring antituberculosis treatment.

Antigens, Bacterial↗

Antibody titres to a rough-mutant strain of Escherichia coli in patients undergoing allogeneic bone-marrow transplantation. Evidence of a protective effect against graft-versus-host disease.

Much clinical and experimental evidence suggests that infection and graft-versus-host disease (GvHD) are commonly associated as complications of bone-marrow transplantation (BMT). A likely basis for this association is the gram-negative faecal flora,the origin of many septicaemias and a source of bacterial endotoxin, which has potent immunostimulatory effects. A rough-mutant strain, Escherichia coli J5, has only core determinants in its endotoxin,and antibodies to E coli J5 protect animals and human beings from the consequences of septic shock. Naturally occurring antibodies to E coli J5 ("anti-endotoxin") were assayed in serum from patients undergoing BMT, healthy controls, and patients with obstructive jaundice. BMT recipients had significantly lower titres than the other two groups. Furthermore, the titre of IgM class anti-J5 antibody was significantly associated with protection from GvHD.

Acute Disease↗

Somatic and autonomic function in progressive autonomic failure and multiple system atrophy.

We studied 62 consecutive patients with progressive autonomic failure (PAF) or multiple system atrophy (MSA) (26 PAF; 36 MSA). Patients were well matched in age (67 vs 66 years), duration (39 vs 36 months), and severity of autonomic failure (median values for PAF and MSA). Peripheral somatic neuropathy occurred in 2 patients with PAF and 7 patients with MSA. Postganglionic sudomotor and vasomotor functions were studied using the quantitative sudomotor axon reflex test and supine plasma norepinephrine. The extent and severity of autonomic failure were assessed by the thermoregulatory sweat test, by heart rate responses to deep breathing and the Valsalva maneuver, and by blood pressure recordings. Severe and widespread anhidrosis was found in both PAF and MSA patients. Postganglionic sudomotor failure occurred at the forearm in 50% each of PAF and MSA patients and at the foot in 69% and 66% of PAF and MSA patients, respectively. However, postganglionic sudomotor function was preserved in some patients with anhidrosis on thermoregulatory sweat test, indicating a preganglionic lesion. Vagal abnormalities were found in 77% and 81% of PAF and MSA patients. Supine plasma free norepinephrine values were significantly reduced in PAF (p less than 0.001), but not in MSA, patients. Standing plasma norepinephrine values were reduced in both PAF (p less than 0.001) and MSA (p less than 0.001) patients. We conclude the following: (1) PAF is characterized by combined postganglionic sudomotor and adrenergic failure. (2) MSA is associated with a similar frequency of postganglionic sudomotor failure, but postganglionic adrenergic denervation was uncommon. (3) Preganglionic neuron is also involved in both disorders, but more severely in MSA. (4) Somatic neuropathy may occur.

Adolescent↗

Infective complications of plasma exchange: a prospective study.

We examined the incidence and types of infective complications which occurred in 41 patients whose medical management included plasma exchange (PX) by intermittent cannulation; femoral, subclavian, or internal jugular catheter; or arteriovenous shunt. A high incidence of positive cultures from vascular access catheters was demonstrated. Of 23 patients for whom data were available, 13 had positive cultures, and results on 3 of these showed greater than 1 species. Gram-positive cocci were typically found. Of the 34 patients who received drug immunosuppression with PX, 1 patient developed severe shunt-site infection, and an additional 4 developed bacteremia. Seven patients were given PX alone, and none of these developed clinically significant infection; however, this difference in infection rate did not reach statistical significance. Clinically significant access-related infection remains an infrequent but potentially important hazard of therapeutic PX.

Adolescent↗

Glucocorticoid induction of beta-adrenergic receptors in the DDT1 MF-2 smooth muscle cell line involves synthesis of new receptor.

We have shown that glucocorticoids induce the appearance of beta 2-adrenergic receptors in membranes of the ductus deferens smooth muscle cell line (DDT1 MF-2). A concomitant increase in isoproterenol stimulated adenylate cyclase activity in the absence of exogenously applied GTP was observed as was a significantly increased (p less than 0.05) sensitivity of the adenylate cyclase system to exogenously applied GTP. However, no significant difference in the maximal velocity of adenylate cyclase between control and steroid treatment was measurable in the presence of sodium fluoride. Induction of beta 2-adrenergic receptors in DDT1 MF-2 cells is correlated with the presence of steroid receptors (androgen and glucocorticoid) in the cells since estrogens and progesterones had no effect on receptor levels. Finally, utilizing dense amino acid labeling of cells to measure old versus newly synthesized receptor sites by a density shift method, we have documented that glucocorticoid induction of beta 2-adrenergic receptors involves synthesis of new receptor protein.

Adenylyl Cyclases↗