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K S Lindsay

Publications and source records attributed to K S Lindsay.

18 recordsLinked to original sources
PubMed1996

The paradoxical effects of pentoxifylline on the binding of spermatozoa to the human zona pellucida.

In the presence of pentoxifylline, human spermatozoa are induced to increase certain motion characteristics; however, the role of this drug in fertilization remains equivocal. In this study, the influence of pentoxifylline on one aspect of fertilization, that is sperm-zona binding, has been examined. Results from a fluorescence label competitive zona binding (CZB) test showed that spermatozoa exposed to a pentoxifylline challenge of between 0.1 and 5 mM, which was curtailed after 1 h by washing, had a decreased (P < 0.01) ability to bind to intact zona compared with control spermatozoa. The washing procedures also removed (decrease P < 0.01 compared with peak values) some of the enhanced motion characteristics induced by pentoxifylline. These results were in contrast with those obtained using experimental conditions that maintained an increased curvilinear velocity (VCL) and lateral head displacement (ALH) (increase P < 0.001 above baseline controls) in the continued presence of pentoxifylline. Using a hemizona binding (HZB) assay, 3 mM pentoxifylline increased (P < 0.001) sperm-zona binding almost 20% above zona binding with unexposed control spermatozoa. It was concluded that, in the presence of pentoxifylline, there is increased sperm binding to the zona pellucida; however, if the drug is removed by washing, the sperm binding to the zona is decreased in concert with the removal of the enhanced motion characteristics. The application of zona solubilization by acidic conditions in a microchamber enabled the precise determination of sperm numbers in both of the sperm-zona binding assays, and the results demonstrated that a wide variation in sperm numbers was observed in each test, with 63-580 spermatozoa bound in the CZB assay and 56-1340 spermatozoa bound on a hemizona.

Female↗
PubMed1996

Factors affecting pentoxifylline stimulation of sperm kinematics in suspensions.

Sperm suspensions were prepared either by the 'swim-up' technique or by a Percoll gradient method before pentoxifylline was added to improve sperm motion characteristics. They were subsequently washed and then incubated with oocytes in in-vitro fertilization (IVF) programmes. The curvilinear velocity and lateral head displacement were approximately 20% higher in Percoll gradient-separated samples compared with samples prepared by the swim-up technique (P > 0.001), sperm motion characteristics being assessed by computer-assisted semen analysis. The dose-response study in which samples were separated by Percoll gradient/swim-up method showed that pentoxifylline gave maximum enhancement of sperm motion characteristics at a concentration of 2.8 mM/l, when the curvilinear velocity and lateral head displacement were significantly increased (P > 0.001). However, when pentoxifylline was removed by washing, the enhanced motion characteristics were reduced or lost in the process. Surprisingly, washing had a significant effect on the control samples, the motion characteristics being increased significantly (P > 0.001). This study casts doubt on the usefulness of pentoxifylline in IVF programmes.

Cell Separation↗
PubMed1996

Increased serum lithium concentration secondary to treatment with tiaprofenic acid and fosinopril.

OBJECTIVE: To describe a patient in whom the administration of tiaprofenic acid and fosinopril was associated with decreased lithium clearance, resulting in increased serum lithium concentrations. CASE SUMMARY: A woman treated with lithium for bipolar affective disorder was concurrently treated with tiaprofenic acid 200 mg tid for shoulder pain. Previously initiated treatment with fosinopril was maintained during this time. The urinary lithium clearance was decreased during this combination therapy, necessitating a reduction in the lithium dosage. DISCUSSION: Lithium is approximately 80% reabsorbed in the proximal tubule, and the addition of tiaprofenic acid may have resulted in enhanced tubular lithium reabsorption. The possible influence of concurrent fosinopril therapy may also have contributed to altered lithium pharmacokinetics in this case. CONCLUSIONS: Serum lithium concentrations should be monitored if patients taking lithium are treated with tiaprofenic acid.

Aged↗
PubMed1995

Action of pentoxifylline directly on semen.

In the presence of pentoxifylline, spermatozoa can be induced to increase certain motion characteristics. This drug capability has been used to study the effect when applied directly on semen. An equal volume of pentoxifylline was added to semen, which was then incubated for 1 h before processing. Sperm motion was assessed employing computer-assisted semen analysis. The results showed that pentoxifylline increased curvilinear velocity, straight line velocity and lateral head displacement, the latter effect being concentration-dependent over the entire range of concentrations tested (r = 0.93, P < 0.0001). With a high concentration of pentoxifylline, spermatozoa exhibited characteristics consistent with hyperactive-like motion. Semen characteristics showed marked interindividual variation, ranging from 0 to > 40% response to 6 mM pentoxifylline challenge. Some 10% of patients showed little or no response to pentoxifylline. The sum of the percentage changes in curvilinear and straight line velocity, lateral head displacement and manual sperm count for each dose group was used to produce the stimulation index, measuring the overall response of spermatozoa to the drug. This stimulation index showed that the most effective concentration was 6 mM pentoxifylline, considerably higher than the 3.6 mM pentoxifylline used commonly for separated spermatozoa.

Dose-Response Relationship, Drug↗
PubMed1995

The variable effects of 2'-deoxyadenosine on human sperm motility and hyperactivation in vitro.

The response of human sperm motility and hyperactivation to the stimulant 2'-deoxyadenosine (2'-DEA) was studied in vitro using computer-assisted sperm motion analysis. A total of 20 randomly selected individuals with normal sperm counts as defined by the World Health Organization were chosen and their migration-separated spermatozoa exposed to a range (0.1-10.0 mM) of concentrations of 2'-DEA. The straight line velocity (VSL) was increased above control values only at 0.1 mM, while the curvilinear velocity (VCL) and lateral head displacement (ALH) were increased significantly at all concentrations. Linearity of progression (LIN), on the other hand, declined with increasing concentration of 2'-DEA. These changes were related to a significant increase in the number of spermatozoa exhibiting hyperactive-like motion. There was, however, considerable intra-individual variability in the response to 2'-DEA. In some individuals VCL and ALH exhibited little or no response to 2'-DEA, whilst in others an increase above the control of 50-55% occurred. The maximum response for VCL and ALH occurred at 2.5 mM 2'-DEA. Individuals showed greater variability in the percentage of spermatozoa exhibiting hyperactivity in response to 2'-DEA, with increases ranging from 76 to 948% of the control value, although the maximum response was also most commonly seen at 2.5 mM 2'-DEA. The diversity of response to 2'-DEA emphasizes the importance of tailoring doses to the individual rather than employing one concentration for all. Further tests on a subgroup of the individuals examined the longevity of spermatozoa in response to 24 h of continued exposure to 2'-DEA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A simple technique to quantify human sperm-zona pellucida binding assays.

A simplified method for assessing the degree of sperm-zona pellucida binding was developed. The zonae pellucidae of salt-stored, failed-fertilized human oocytes were each inseminated with between 1 x 10(5) and 1 x 10(6) motile spermatozoa/ml, prepared by a direct swim-up method from 11 individuals with normal sperm counts, as defined by the World Health Organization. Following 4 h of incubation at 37 degrees C in humidified air, the zonae pellucidae were 'washed' by vigorous pipetting to remove any loosely attached spermatozoa. The zonae were then placed individually in microwells and dissolved by exposure to acidified (pH < 2.0) medium to form a fluid monolayer. The slides were sealed and the number of spermatozoa in the monolayer counted by each of three observers within 24 h. There was good agreement in the counts between the different observers, with a mean coefficient of variation of only 7.4% and a range of 1.8-16.7%. It was notable that the highest coefficients of variation occurred at the extremes of sperm numbers and that the results were stable overnight. The method is also able to identify observer bias within this variation, indicating the potential for improvements in assay performance. The technique reported has the advantage over current sperm-zona pellucida binding assays of allowing the determination of the precise number of spermatozoa bound to a zona pellucida while producing a slide which remains stable overnight.

Biological Assay↗
PubMed1995

Spermatozoa selected by a discontinuous Percoll density gradient exhibit better motion characteristics, more hyperactivation, and longer survival than direct swim-up.

OBJECTIVE: To determine if a discontinuous Percoll density gradient selects spermatozoa with different motion characteristics than direct swim-up. DESIGN: Controlled prospective study of the effect of two preparation techniques on spermatozoa from normal semen samples using computer-aided sperm analysis (CASA). SETTING: The Fertility laboratory, Queen Charlotte's Hospital, London, United Kingdom. PATIENTS: Eighteen male patients. INTERVENTIONS: Semen samples were divided into two equal parts. The first part was prepared by a direct swim-up whereas the other half was subjected to a three-layer discontinuous Percoll density gradient centrifugation. The separated samples were then examined at 30 minutes and 3, 6, and 24 hours by CASA. RESULTS: Although swim-up selected a higher proportion of motile spermatozoa, Percoll produced a greater yield of motile cells. Straight line velocity was similar for both methods throughout study. In contrast, spermatozoa isolated by Percoll exhibited a significantly higher curvilinear velocity and amplitude of lateral head displacement, which lasted for > or = 6 hours. These changes were accompanied by a significant reduction in linearity of progression. The most dramatic effect of Percoll was to produce significantly greater numbers of spermatozoa expressing hyperactivation. After both swim-up and Percoll there was a decline in progressive motility over the 24 hours, although this was only significant for swim-up. CONCLUSIONS: In normal semen, a discontinuous Percoll density gradient selects spermatozoa with better motion characteristics, more hyperactivation, and improved longevity compared with direct swim-up. In view of the relationship between sperm motion characteristics and fertilizing ability, we conclude that the three-layer discontinuous Percoll density gradient be adopted as the preferred method for the preparation of spermatozoa for assisted reproduction.

Adult↗
PubMed1994

Fertility in men with primary ciliary dyskinesia presenting with respiratory infection.

BACKGROUND: Primary ciliary dyskinesia is characterised by chronic rhinosinusitis, chronic bronchial sepsis (usually with bronchiectasis), dextrocardia in approximately 50% of cases, and male infertility. The latter, described in patients attending infertility clinics, results from immotile but viable spermatozoa. Experience in a respiratory clinic suggests that infertility in men is not invariable. METHODS: The seminal fluid of 12 men with primary ciliary dyskinesia, six with dextrocardia, who presented consecutively with upper and lower respiratory tract sepsis was examined. Nasal ciliary beating was dyskinetic or absent in all cases, and nasal ciliary ultrastructure was abnormal in those 11 patients examined. RESULTS: Viable but immotile spermatozoa with abnormal tail ultrastructure were found in the ejaculate of only two patients. Two other patients had apparently fathered children; seminology in both these cases showed a normal spermatozoa count, one with normal spermatozoal motility and normal ultrastructure, the other with moderately reduced spermatozoal motility and abnormal ultrastructure (dynein arm deficiency on the peripheral microtubule doublets). A further two patients had normal spermatozoa counts, normal spermatozoa tail ultrastructure, and normal or only moderately reduced motility of spermatozoa. The spermatozoa of one patient were normally motile but there was severe oligozoospermia, and five patients were azoospermic. CONCLUSIONS: Not all men with primary ciliary dyskinesia have immotile spermatozoa. Seminal analysis is recommended in men with primary ciliary dyskinesia so that accurate counselling about reproductive capability may be given.

Adolescent↗
PubMed1993

Variability of human sperm response to immediate and prolonged exposure to pentoxifylline.

Pentoxifylline improves some motility characteristics of human spermatozoa, but the variability of response to this drug has not been clearly defined. We used computer-assisted sperm motion analysis to examine the in-vitro response of spermatozoa to pentoxifylline. Individuals (n = 31) with normal sperm counts were randomly selected and their spermatozoa exposed to different concentrations of pentoxifylline. Further tests on a subgroup of individuals examined the longevity of spermatozoa in response to this agent. Straight line velocity (VSL) was only improved at 0.1 mM and the major effect of the drug was on curvilinear velocity (VCL) and lateral head displacement (ALH). Prolonged exposure to pentoxifylline enhanced sperm motion only at 0.1 mM. Higher concentrations produced dose-dependent detrimental effects on all the motion characteristics. There was considerable inter-individual variability in both VCL and ALH response ranging from little or no detectable response to a 40% increase above control value. The maximum response was most commonly seen at a concentration of 2 mM pentoxifylline.

Humans↗
PubMed1993

Effects of plasma exchange on sperm antibody levels in males with subfertility.

Three men with subfertility secondary to sperm antibodies with measurable serum sperm antibody levels underwent a course of 3 plasma exchanges over a period of 1 week. The levels of serum anti-sperm antibodies fell by a mean of 3.3 dilutions. This fall was maintained for approximately 4 weeks, after which there was a return to the original levels. Plasma exchange is time-consuming and relatively expensive but it offers a possible alternative to steroid treatment (with its potential side effects) in men with sperm antibodies and warrants further investigation.

Adult↗
PubMed1989

Semen cryopreservation in men undergoing cancer chemotherapy--a UK survey.

A questionnaire was sent to all centres in the UK involved in cryopreservation of semen from men with malignant disease. Details were requested of samples stored from 1977 to 1987 and of successful use of this sperm in subsequently achieving pregnancy. Twenty-two centres are involved and have stored specimens from 2,219 men. There has been a three-fold increase in referrals in the past five years. Three regions in England have no service. Twenty-seven pregnancies (21 live births) have been achieved in 22 couples. Laboratories are poorly funded, making adequate record keeping and audit of the service difficult.

Cryopreservation↗
PubMed1989

Extended exposure to follicular fluid is required for significant stimulation of the acrosome reaction in human spermatozoa.

The effect of human follicular fluid (FF) on the incidence of spontaneous acrosome reactions (AR) in human spermatozoa was examined over a 24-25 h period using electron microscopy. Suspensions of motile spermatozoa were prepared by a swim-up method in Earle's medium, known to support in-vitro fertilization. After adjusting the concentration to 10 x 10(6) cells/ml, suspensions were diluted 1:1 with medium (control) or FF, the latter giving a final concentration of 50% FF. In addition, at 5 h and 24 h an aliquant of the control suspension was removed, diluted 1:1 with FF and incubated for 1 h; the three suspensions were examined at 6 h and 25 h. Continuous exposure to 50% FF stimulated the AR, the effect being significant (P less than 0.001) at 25 h. However, the 1-h short exposure of spermatozoa to FF did not produce an increase in AR, even after 24 h preincubation. In a separate series of experiments, the effect of continuous incubation for 24 h in increasing concentrations of FF was investigated. A significant linear dose-dependent effect on the AR was observed with all concentrations assessed (P less than 0.01 for 12.5% FF and P less than 0.001 for 25, 50, 75 and 100% FF, compared with FF-free control). Therefore, human FF can stimulate the AR, but only after a continuous exposure to FF. A short exposure to FF, even after 24 h preincubation, does not trigger an increased AR response.

Acrosome↗
PubMed1989

Human oocyte-cumulus complexes stimulate the human acrosome reaction.

Oocyte-cumulus complexes were obtained, after induced ovulation, from infertile patients participating in an in-vitro fertilization programme. About 6 h after retrieval and depending on the expansion of the cumulus, 100,000 motile spermatozoa, prepared by a migration-centrifugation method, were added. After 14-18 h incubation at 37 degrees C, oocytes were examined for signs of fertilization (pronuclei and polar body formation) and then removed; spermatozoa remaining in the incubation medium were fixed for transmission electron microscopy. To provide an adequate number of cells for observation, spermatozoa from a minimum of 3-5 oocytes from the same patient were pooled. When sufficient spermatozoa were available after insemination, the remainder of the suspension was incubated at 37 degrees C and fixed along with the corresponding oocyte-incubated sample. In all, 32 sperm samples were assessed and fertilized oocytes were obtained with 29 of these. In the 24 samples in which greater than 100 spermatozoa (mean of 192) could be assessed, 32% of spermatozoa had initiated or completed the acrosome reaction. In the 15 of these 24 samples for which oocyte-free controls were available, 31% of cells were reacting or reacted, compared with 15% of cells (P less than 0.001) in the controls. In the remaining 8 samples, incubated with oocyte-cumulus complexes, less than 100 but greater than or equal to 20 spermatozoa (mean of 42) were assessed and again 32% of spermatozoa were reacted.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1988

Programmed gamete intrafallopian transfer (GIFT).

Thirty-three patients with unexplained infertility underwent a total of 42 programmed superovulation cycles in a gamete intrafallopian transfer (GIFT) programme. The date of oocyte retrieval was decided in advance and the cycle preceding oocyte collection was modified with norethisterone from mid-cycle until 14 days before the scheduled laparoscopy. This was followed by a fixed schedule superovulation regimen. Serum oestradiol, progesterone and luteinizing hormone were monitored and the data analysed retrospectively. A single ultrasound scan was performed on the day of laparoscopy to exclude ovulation. Thirty-eight GIFT procedures were performed, resulting in 11 (29%) clinical pregnancies of which four twin and four singleton pregnancies are continuing. There was a significant correlation between the oestradiol response pattern and the maturity of oocytes retrieved, the fertilization rate of supernumerary oocytes and the pregnancy rate. Programmed cycles may be conveniently combined with GIFT, and basic endocrinological monitoring can be used to identify cycles with a poor prognosis before laparoscopy.

Adult↗
PubMed1982

Early embryonic mortality in women.

Measurements of human chorionic gonadotropin (hCG) have been used to assess early embryo loss in women. Urine samples obtained from a control group of sterilized women with normal ovulatory menstrual cycles enabled a concentration limit of 56 IU/l to be determined so that any nontrophoblastic hCG or other cross-reacting compounds could be accounted for. One hundred ninety-eight ovulatory cycles were collected from a normal population attempting to conceive. Fecundability was 22% to 27% for this population. The risk of pregnancy in exposed ovulatory cycles was 59.6%; however, 61.9% of conceptuses will be lost prior to 12 weeks. Most of these losses (91.7%) occur subclinically, without the knowledge of the mother.

Adult↗
PubMedDate not supplied

Induction of labour in sheep after fetal hypophysectomy: an investigation of the possible involvement of a fetal pituitary secretion in the activation of placental enzymes by fetal cortisol.

Activities of 17 alpha-hydroxylase, C-17, 20 lyase and aromatase were measured in placentae of intact and hypophysectomized fetuses after premature induction of parturition by fetal administration of Synacthen. Activities of these enzymes were compared with concentrations of steroids produced by the placenta, which were measured in maternal plasma before and during parturition. Hypophysectomy was assessed by determining fetal plasma concentrations of LH before and after administering LH-RH, and histologically post partum. Concentrations of progesterone, which decreased before parturition, and of 17 alpha, 20 alpha-dihydroxypregn-4-en-3-one and oestradiol-17 beta, which increased, were not affected by fetal hypophysectomy. However, fetal hypophysectomy reduced the normal rise in oestrone sulphate which precedes parturition and abolished the normal rise in androstenedione. Although placental activities of C-17, 20 lyase and aromatase (but not 17 alpha-hydroxylase) tended to be reduced by fetal hypophysectomy, these effects were not statistically significant. The data support an earlier suggestion that an unidentified product of the fetal pituitary may be involved in the activation of C-17, 20 lyase by fetal cortisol before parturition. However, the results of the present study show that the action of such a factor is more likely to be permissive than obligatory.

Aldehyde-Lyases↗