Women and AIDS.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J Cohen
Publications and source records attributed to J Cohen.
Comorbidity of psychiatric diagnoses in anorexia nervosa.
The comorbidity of psychiatric diagnoses was examined with the Diagnostic Interview Schedule in 62 women who participated in a 10-year follow-up study of anorexia nervosa. Sixty-two age- and sex-matched controls, their parents, and parents of the anorectic probands were also interviewed with the Diagnostic Interview Schedule. There was a statistically significant comorbidity of the affective and anxiety disorders with anorexia nervosa. The first-degree relatives of the anorectic probands had significantly more alcoholism and total number of psychiatric diagnoses compared with the first-degree relatives of controls. There were two mothers with bulimia nervosa, two cases of anorexia nervosa and two of bulimia nervosa in other first-degree relatives of anorectic probands, and no cases of eating disorders in the first-degree relatives of controls.
Adult↗
Visual dysfunction in Alzheimer's disease: relation to normal aging.
In patients with Alzheimer's disease (AD), compared with age-matched and young healthy control subjects, visual deficits in the following functions were observed: color, stereoacuity, contrast sensitivity, and backward masking (homogeneous and pattern). Critical flicker fusion thresholds were normal, relative to age-matched healthy subjects. For color, the majority of the errors were tritanomalous (blue axis). Color and stereoacuity deficits were unrelated to severity of dementia, in accordance with models of vision that describe these functions as modular rather than diffuse for cortical localization. Although contrast sensitivity was depressed throughout the frequency range in AD, more patients were impaired at low than at high spatial frequencies, contrasting with the observed normal aging pattern of high-frequency loss. Healthy elderly subjects showed depressed critical flicker fusion thresholds and reduced contrast sensitivity at high frequencies, relative to the young group; differences between these groups were not found for the other vision tests. A subset of the AD group received detailed neuro-ophthalmological examination, and no abnormalities were found. This finding, taken together with normal thresholds for critical flicker fusion, suggests that the widespread visual dysfunction reported here is more likely to be related to known pathological changes in primary visual and association cortex in AD than to changes in the retina or optic nerve.
Adolescent↗
Experimental models of plasma perfusion.
A system allowing repeated plasma perfusion in the unrestrained conscious rat was developed in order to examine the effects of plasma filtration with on-line sorbent treatment of plasma in various models of disease. In experimental autoimmune glomerulonephritis, perfusion over a column coated with glomerular basement membrane (GBM) antigen lowered circulating levels of anti-GBM antibodies. In experimental endotoxaemia, perfusion over a column coated with polymixin B (PB) lowered circulating endotoxin levels and protected animals from haematological abnormalities and death. In experimental acute hepatic failure, perfusion over a combination of charcoal, resin, and PB columns improved survival in grades II and III hepatic coma. This experimental system has allowed preclinical evaluation of the effectiveness of different sorbents in the treatment of a range of disorders.
Animals↗
A preferential site for sperm-egg fusion in mammals.
The tendency of mammalian sperm-egg fusion to occur at a site away from the first polar body was investigated in a homologous (mouse oocytes and mouse spermatozoa) and in a heterologous model (hamster oocytes and mouse spermatozoa). Following micromanipulation of the zona pellucida either in proximity to or opposite the first polar body, in vitro fertilization was performed and subsequent differences in sperm-egg interaction were evaluated. Since spermatozoa from random-bred mice do not readily penetrate intact zonae pellucidae in vitro, it is likely that zona penetration occurred through the artificial holes in both models. The creation of a gap in the zona pellucida opposite the first polar body was associated with levels of sperm fusion that were significantly higher than those resulting from manipulation near the first polar body. Spermatozoa were rarely found to penetrate the hole completely, and in general few spermatozoa were observed in the pervitelline space. The proximity between pronuclei following sperm penetration was correlated with the position of the incision with respect to the polar body. The findings suggest that breaching the zona pellucida for microsurgical fertilization should be performed away from the microvillus-free area of the oocyte.
Animals↗
Effects of the size and number of zona pellucida openings on hatching and trophoblast outgrowth in the mouse embryo.
The present studies were performed to establish the effects of the size and number of artificial holes produced in the zona pellucida (ZP) on hatching and trophoblast outgrowth in vitro. Limited partial zona dissection (PZD) produced small, narrow incisions, and zona drilling with acidic Tyrode's (AT) across a larger area in the ZP was used to produce bigger round holes. Some embryos were micromanipulated once; others were micromanipulated several times. Blastocysts hatched preferentially through the artificial gaps, but completion of hatching was dependent on the size of the hole. Only 16% (26/167) of PZD embryos migrating through narrow holes hatched completely; the remainder were trapped in a typical figure-eight shape. Seventy-two percent (43/60) of those migrating through larger PZD holes hatched, but trophoblast outgrowth was not observed. Significantly (P less than 0.001) more AT-blastocysts hatched (248/270; 92%) and showed trophoblast outgrowth (176/248; 70%). Simultaneous hatching through several openings was rarely observed in AT-embryos (14/167; 8%), but this did occur in 36% (73/201) of the PZD embryos. Trapping of PZD-embryos could be almost entirely avoided by drilling with AT elsewhere on the ZP. Embryos with multiple holes in their zonae preferentially hatched through the largest opening. The results suggest that the ability of microsurgically treated human embryos to fully hatch in vitro, should be carefully (re)assessed prior to application of clinical micromanipulation systems. Micromanipulated embryos with small holes in their zonae may be rescued by performing an additional more aggressive opening procedure elsewhere on the ZP.
Animals↗
Assisted hatching of human embryos.
There are benefits as well as drawbacks of zona pellucida breaching. Narrow gaps in the zona may cause disintegration of the hatching trophectoderm, when embryos are cultured in vitro. An increase in the formation of monozygotic twins following micromanipulation may also occur, due to the forced separation of the inner cell mass during blastocyst expulsion in utero. Mouse studies indicate that one or several narrow zona openings (less than 5 microns) are detrimental. Such embryos may become trapped during hatching but may be rescued by drilling an additional larger gap elsewhere on the zona. The use of acidic Tyrode's solution for clinical assisted hatching of eight-cell embryos is currently under investigation. The findings suggest that large holes are efficient for promoting hatching (at least one-fourth of the embryos implanted thus far) and that embryos with unthinned zonae (those with normally the poorest prognosis) benefit mostly from assisted hatching. Results also indicate that embryos with the best zona morphology should be replaced without micromanipulation.
Animals↗
Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis.
Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic. Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography. There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points. Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic. The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora. This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection.
Adult↗
Partial dissection of the zona pellucida of frozen-thawed human embryos may enhance blastocyst hatching, implantation, and pregnancy rates.
The rate of successful implantation after replacement of frozen-thawed embryos in in vitro fertilization is commonly only 5% to 10% per embryo. A limiting factor may be inability of otherwise viable embryos to be released from the intact zonae pellucidae. Culture conditions and/or cryopreservation in in vitro fertilization may affect the zona and impair blastocyst hatching. Therefore opening of the zona by partial slicing by means of micromanipulation before replacement of early cleaved embryos may improve chances of eventual hatching (referred to as assisted hatching). In 65 thawed embryo replacement cycles methyl-prednisolone and antibiotics were given for 4 days mid cycle. Assisted hatching was performed in 32 cycles, with 33 cycles left as controls. Patient's age, infertility, cycle supplementation, and number of thawed and replaced embryos did not differ significantly between the two groups. Rates of viable embryonic implantation were 16% (10/63) and 9% (6/64) in the assisted hatching and control groups, respectively. Group sizes need approximately to double before this trend toward improved implantation with the use of assisted hatching reaches statistical significance.
Adult↗
Percutaneous transperineal prostate cryosurgery using transrectal ultrasound guidance: animal model.
Cryosurgery has previously been used successfully to treat prostatic carcinoma. Inability to monitor the freezing led to local complications that limited the use of this modality. Recent studies have shown that monitoring of the freezing process can be accomplished using real-time ultrasound. In this study, transrectal ultrasound guidance was used to guide a cryoprobe percutaneously, using a transperineal approach, into the prostate. The extent of freezing was then monitored using ultrasound, taking care not to freeze the urethra or the rectum. Six dogs had the procedure without any complications. This study demonstrates the feasibility of a noninvasive treatment for prostatic carcinoma.
Animals↗
Stimulation cycles suppressed with gonadotropin-releasing hormone analog yield accelerated embryos.
A retrospective study was performed to assess embryonic development and morphology in 71 patients whose follicular stimulation was regulated after down regulation with a gonadotropin-releasing hormone analog, leuprolide acetate. The embryos were compared with those from 66 patients who did not receive agonists and who were treated during the same period. A separate group of thawed embryos cryopreserved after down regulation in 21 patients was compared with embryos frozen after conventional stimulation during the same period from 21 other patients. Eleven morphological criteria were assessed in the fresh embryos, and analyses did not reveal any differences between the groups studied. However, the rate of development of embryos obtained during down-regulated cycles was significantly higher than that of embryos developing in conventional stimulation cycles. Although no significant morphological differences could be shown between the groups of cryopreserved embryos, there was a decreased incidence of implantation of embryos from patients who were exposed to analogs. It is suggested that embryos from down-regulated cycles should be cryopreserved earlier to correct for their accelerated development.
Clomiphene↗
Partial zona dissection or subzonal sperm insertion: microsurgical fertilization alternatives based on evaluation of sperm and embryo morphology.
OBJECTIVE: To establish guidelines for application of partial zona dissection, subzonal sperm insertion, and regular in vitro fertilization (IVF) in severe male factor patients. DESIGN: Two studies were performed: partial zona dissection and IVF was applied in 57 couples during the first period, and subzonal sperm insertion was also applied in a second group of 47 couples. SETTING: Procedures were performed in an academic research environment. PATIENTS, PARTICIPANTS: Couples who failed fertilization previously, others not acceptable for IVF, and a third group in whom IVF was expected to fail. INTERVENTIONS: Oocytes were micromanipulated with either partial zona dissection or subzonal sperm insertion, or the zona pellucida was left intact. Embryos were replaced in patients prophylactically treated with methylprednisolone and antibiotics. MAIN OUTCOME MEASURES: Because several microsurgical fertilization techniques are now available, this study was performed to compare sperm parameters, embryo morphology, fertilization, and implantation rates after application of two successful micromanipulation procedures. RESULTS: Twenty-one pregnancies were established in 104 patients, 5 definitely from subzonal sperm insertion and 4 from partial zona dissection. Patients who failed IVF before had a similar chance of pregnancy after the use of micromanipulation, as first time patients (9/53 versus 12/51). In a subgroup of 15 patients who failed IVF with insufficient numbers of motile sperm, fertilization was significantly higher after subzonal sperm insertion. Partially zona-dissected embryos from couples with severe teratozoospermia (less than or equal to 5% normal forms; strict criteria) had significantly more morphological abnormalities than those from patients with moderate teratozoospermia (6% to 10% normal forms). In severely teratozoospermic patients, significantly fewer partially zona-dissected than subzonally inserted embryos implanted. CONCLUSIONS: The decision of which micromanipulation method to perform can possibly be based on careful analysis of sperm morphology.
Embryo Implantation↗
Axon guidance in the vertebrate central nervous system.
The development of connections in the central nervous system depends on the ability of the tips of growing axons to find their appropriate, often distant, target field. Factors that regulate axon outgrowth may be distinct from those that influence direction finding. Tissue culture methods have helped to distinguish between possible in vivo mechanisms and, in some cases, have identified candidate molecules.
Animals↗
Design of a well-absorbed renin inhibitor.
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Alanine↗
Clinical management of fungal infection in patients with AIDS.
The frequency of disseminated fungal infection in patients with the Acquired Immune Deficiency Syndrome (AIDS) has provided a major impetus for the reevaluation of standard antifungal protocols as well as accelerating the development and clinical testing of new agents. As a result, useful clinical guidelines regarding the use of amphotericin B and flucytosine in cryptococcosis are beginning to emerge that relate specifically to patients with AIDS. Oral agents, most notably fluconazole have shown promise and are now being evaluated in controlled clinical trials. Histoplasmosis and coccidioidomycosis have emerged as significant infections and pose new problems in both diagnosis and management. Although amphotericin B and flucytosine must still be used for induction therapy in patients with these infections, preliminary studies of itraconazole suggest that it could be useful for maintenance therapy. Despite there being considerably less clinical experience with histoplasmosis and coccidioidomycosis than with cryptococcosis, it is hoped that the lessons learnt with cryptococcosis will accelerate the development of new diagnostic assays and improved therapeutic approaches.
Acquired Immunodeficiency Syndrome↗
Microsurgical fertilization and teratozoospermia.
Semen parameters were correlated with the outcome of partial zona dissection (PZD) in 42 couples with male factor infertility. Although fertilization rates were reduced, 12% of the embryos implanted following replacement. Spermatozoa from teratozoospermic sperm populations were able to fuse with oocytes following zona penetration through the artificial gaps. PZD followed by insemination with less than 5% normal spermatozoa led to 20 embryos which, upon replacement, did not implant. Motility and sperm count were not clearly correlated with the outcome of PZD and are therefore less useful indicators for patient selection. Teratozoospermic patients who previously failed to fertilize were compared to a group of similar patients who had not attempted IVF before. Although fertilization was significantly improved in first-time patients, 41% of the patients whose spermatozoa were initially unable to fertilize had at least one embryo when PZD was performed. Several pregnancies were established in this group. Subzonal sperm insertion (SZI) and PZD were compared in 19 patients using sibling oocytes. A significant fraction of spermatozoa from infertile men were able to fuse with the oolemma when directly inserted into the perivitelline area. Using a sucrose solution to shrink the ooplasm, only 1% of the oocytes were damaged during SZI. Monospermic fertilization rates following PZD and SZI were 15 and 16%, respectively. Both micromanipulation methods were successful in most patients. However, in two small groups of patients, only one technique resulted in fertilization.
Female↗
The efficiency and efficacy of IVF and GIFT.
Data relating to the rate of clinical pregnancy obtained with in-vitro fertilization--embryo transfer (IVF-ET) and gamete intra-Fallopian transfer (GIFT) are available for Australia, UK, USA and France. For IVF-ET the value is not affected by the indication but is affected by the age of the woman. The rate of spontaneous abortion, at approximately 20-25% also increases with age and is an important consideration in view of the increased age of patients undergoing IVF-ET. A take-home baby rate of 30% is obtained from an estimated 70% of clinical pregnancies leading to live births and an estimate of 42.8% pregnancies after three attempts. The greater number of oocytes transferred with GIFT may be associated with the increased frequency of multiple pregnancies.
Australia↗
Routine application of partial zona dissection for male factor infertility.
Partial zona dissection (PZD) increases the chances of fertilization by improving the access of spermatozoa to the perivitelline space (PVS) helping those spermatozoa unable to penetrate the zona pellucida (ZP) and possibly those poorly able to penetrate the oolemma. Problems arise in assessing semen to decide which parameters might indicate defects of this nature. PZD, by circumventing the ZP, may also increase the rate of polyspermy, especially in infertility where ZP and oolemmal penetration are not defective. Given these drawbacks, we performed PZD as routine treatment for male infertility in 70 in-vitro fertilization cycles. In three different groups, PZD proved to be either effective, ineffective or unnecessary. In the first group of 35 cycles, fertilization was 23% with initial PZD and 33% with PZD reinsemination (36% and 41% polyspermy respectively). No fertilization occurred following conventional insemination (CONV). Four pregnancies occurred in this group. In a second group of 19 cycles, fertilization did not occur with either PZD or CONV. In the final group of 16 cycles, fertilization was similar following both PZD and CONV, but polyspermy was 48% in the PZD category. Transfer of mixed PZD and CONV embryos in this group yielded 10 pregnancies. Assessment of all patient and seminal profiles, and those in an oligozoospermic subcategory, revealed no parameters of relevance to success or failure with PZD. However, one subgroup in the group of total failure to fertilize did have a significantly lower percentage of normal morphology (P less than 0.005), suggesting that degree of teratozoospermia may be a prognosticator of success using PZD.
Female↗