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R J Aitken

Publications and source records attributed to R J Aitken.

At least 91 records · Page 5Linked to original sources
PubMed1996

Should consultant surgeons see new or follow-up patients? A prospective audit of a change in clinic organisation.

In the traditional surgical clinic consultants assess new referrals (NP) and trainees follow-up patients (FP). To improve the management of FP and to increase trainee teaching a clinic was changed so trainees assessed NP (under supervision) and the consultant FP. A prospective audit was conducted two months before and two and six months after the change. A further audit four years later included a questionnaire to trainees, patients, General Practitioners (GP) and nurses. Before the change the proportion of NP to FP was 1:1.9. Six months later FP were reduced by 28 per cent. Four years later the proportion of NP to FP was 1:1.6. The consultant was more likely to discharge follow-up patients and shortened the interval between follow-up appointments. Questionnaires revealed that many GPs (59 per cent) would accept less consultant involvement with NP if this increased FP discharges. All trainees and most nurses (83 per cent) preferred the rearranged clinic. NP found initial assessment by trainees acceptable and FP noted the greater consultant input. This study suggests that consultant surgeons should review more FP and this can be achieved without reducing NP consultations. This arrangement is acceptable to patients and improves training. Guidelines recommending that consultants see all NP should be reconsidered.

Attitude of Health Personnel↗
PubMed1996

Evaluation of zona pellucida antigens as potential candidates for immunocontraception.

Antibodies directed against the zona pellucida can interrupt sperm-egg recognition in vitro. However, the mechanisms by which anti-zona antibodies exert this contraceptive effect in vivo remain uncertain. There is an accumulating body of evidence to suggest that active immunity against zona antigens not only induces infertility via an antibody-mediated interruption of sperm--egg interaction but also disrupts normal ovarian function. We have evaluated the consequence of inducing active immunity against purified recombinant human ZP3 (rec.hZP3) and human ZP3 peptides, using the marmoset monkey, Callithrix jacchus, as an animal model. Although infertility was established in animals that received rec.hZP3, it was associated with ovarian dysfunction characterized by suppression of folliculogenesis and depletion of the primordial follicle pool. Immunization with continuous human ZP3 peptides, identified by epitope mapping studies, did not induce ovarian pathology but the antibody titres were insufficient to suppress fertility significantly and consistently. Clearly, further research is required to identify and segregate epitopes on the zona glycoproteins that are capable of inducing infertility without any side effects.

Animals↗
PubMed1995

Complementary effects of propranolol and nonoxynol-9 upon human sperm motility.

The inhibitory effects of nonoxynol-9, DL- and D-propranolol upon human sperm motility were determined in vitro. All three compounds were capable of causing complete cessation of sperm movement. However, greater efficacy was achieved using combinations of nonoxynol-9 and propranolol, suggesting a complementary interaction between these compounds. Investigations of the mechanism of action of propranolol revealed that an influx of calcium accompanied the loss of motility. However, since incubation in the absence of calcium enhanced the spermicidal effects of this compound, it was concluded that this calcium influx did not constitute the primary means by which motility was disrupted. Low doses of propranolol, which did not affect motility, were found to inhibit the capacity of human spermatozoa for sperm-oocyte fusion.

Calcium↗
PubMed1995

Predicting the fertilizing potential of human sperm suspensions in vitro: importance of sperm morphology and leukocyte contamination.

OBJECTIVE: To determine the relationships between sperm function tests and fertilization of human oocytes in vitro. DESIGN: Analysis of infertile patients undergoing IVF therapy. SETTING: Diagnostic Andrology Laboratory and Assisted Conception Service. PATIENTS: Forty-one couples who underwent IVF-ET therapy were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The ability of human spermatozoa to achieve fertilization in vitro was examined in relation to numerous criteria of semen quality, including the conventional semen profile, the computer-aided assessment of sperm movement, ionophore-induced acrosome reaction, acridine orange staining, sperm morphology, and chemiluminescent signals induced by phorbol ester and N-formyl-methionyl-leucyl-phenylalanine (FMLP). RESULTS: Significant correlations were observed between fertilization rates and several attributes of the sperm preparations, including elements of sperm function (acrosome reaction), movement (percentage motile, hyperactivation, the amplitude of lateral sperm head displacement), morphology (normal morphology, midpiece defects, multiple anomalies index), nuclear normality (acridine orange staining), and reactive oxygen species generation (chemiluminescence induced by phorbol ester and FMLP). In a stepwise multiple regression analysis, an accurate prediction of fertilization rates was obtained using a multiple regression equation incorporating six variables of which sperm morphology and FMLP-induced chemiluminescence were the most informative. CONCLUSIONS: A set of criteria have been identified that accurately predict the fertilizing potential of human sperm suspensions in vitro and that place particular emphasis on sperm morphology and the degree of leukocyte contamination.

Acridine Orange↗
PubMed1995

Free radicals, lipid peroxidation and sperm function.

The cellular generation of reactive oxygen species was first observed in mammalian spermatozoa in the late 1940s. The field then remained dormant for 30 years until Thaddeus Mann and Roy Jones published a series of landmark papers in the 1970s in which the importance of lipid peroxidation as a mechanism for damaging mammalian spermatozoa was first intimated. The subsequent demonstration that human spermatozoa produce reactive oxygen species and are susceptible to peroxidative damage has triggered intense interest in the role of oxidative stress in the aetiology of male infertility. Moreover, data have recently been obtained to indicate that, although excessive exposure to reactive oxygen species may be harmful to spermatozoa, in physiological amounts these molecules are of importance in the control of normal sperm function. This review considers the dualistic role of reactive oxygen species and sets out the current understanding of the importance of oxidative processes in both the physiology and the pathology of the human spermatozoon.

Free Radicals↗
PubMed1995

Workshop report: clinical CASA--the quest for consensus.

The goals of the Workshop were to establish the current state-of-the-art in the clinical use of computer-aided sperm analysis (CASA), to identify areas of contention or confusion in the use of CASA technology, and to reach consensus on these matters to facilitate the wider use, and usefulness, of these instruments in clinical and research applications. CASA assessments of sperm morphology were not considered as they were discussed in a separate Workshop (Advanced Techniques in Sperm Preparation and Imaging) on analytical techniques. Four topics were considered: (a) CASA and semen analysis; (b) the diagnostic value of sperm kinematics in semen; (c) human sperm hyperactivation; and (d) CASA and fertility prediction. In all, 17 specific consensus points were identified.

Biomechanical Phenomena↗
PubMed1995

Definition of the optimal criteria for identifying hyperactivated human spermatozoa at 25 Hz using in-vitro fertilization as a functional end-point.

Spermatozoa from fertile donors were used to select and validate criteria for the automated classification of hyperactivated (HA) motility using a computer-aided sperm analysis (CASA) system operating at 25 Hz. In the first phase of this analysis, 710 sperm trajectories were analysed and classified as forward progressive (FP), transition phase (TP) or HA. These tracks were then subjected to a CASA analysis and the various attributes of sperm movement defined for each category of motion. From this analysis, criteria were identified and subsequently validated that permitted the automated selection of FP, TP+HA and HA cells, with > 90% accuracy. To determine which attributes of movement best predicted the fertilizing potential of human spermatozoa, a detailed analysis of sperm motion was undertaken in patients undergoing in-vitro fertilization therapy. This analysis indicated that the single most important aspect of sperm movement was the incidence of HA motility (defined as curvilinear velocity > 90 microns/s, linearity < 20%, dancemean [amplitude of lateral head displacement/linearity x 100] > 45.8 microns) after 3 h of incubation. Using the latter criterion as the first incorporated variable, multiple regression equations were created that explained up to 50% of the variance in fertilization rates. None of the other patterns of motion (FP, TP, TP+HA) was correlated with fertilization rates, and none of the other published algorithms for identifying HA cells were as efficient as those described here.

Cohort Studies↗
PubMed1995

Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma.

The addition of luminol to unprocessed semen samples resulted in the generation of chemiluminescent signals, the intensity of which was highly correlated with the level of leukocyte contamination. Despite the spontaneous oxidant-generating capacity of seminal leukocytes, no correlations were observed between leukocyte contamination and the fertility status of the subjects or any aspect of the semen profile, including the motility of the spermatozoa or their performance in a hyaluronate penetration assay. Luminol-dependent chemiluminescence and leukocyte contamination were also correlated in washed sperm suspensions prepared either by repeated centrifugation or on discontinuous Percoll gradients. However, in such sperm suspensions, the spontaneous generation of oxidants by contaminating leukocytes (> 2 x 10(4) leukocytes/ml) was invariably associated with a decreased capacity for movement. Moreover, causative associations between leukocyte contamination, reactive oxygen species generation, lipid peroxidation and impaired sperm motility were revealed by experiments involving the selective addition or removal of activated leukocytes. From these observations we can conclude that low concentrations of leukocytes are a common feature of the human ejaculate and can impair sperm function, particularly in the absence of seminal plasma. These findings have implications for our understanding of the importance of leukocytospermia in defining the fertility of human spermatozoa in vivo and in vitro.

Antibodies, Monoclonal↗
PubMed1995

Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function.

The redox status of human spermatozoa was found to have a profound influence on the fertilizing potential of these cells in association with qualitative and quantitative changes in the patterns of tyrosine phosphorylation. In general, oxidizing conditions enhanced tyrosine phosphorylation and stimulated sperm function, whereas reducing conditions had the opposite effect. Unstimulated human spermatozoa exhibited low levels of spontaneous acrosomal exocytosis and sperm-oocyte fusion and minimal reactive oxygen species generation, while phosphotyrosine expression was largely confined to a single protein of 116 kDa. However, if the spermatozoa were exposed to oxidizing conditions through the addition of exogenous H2O2, or the stimulation of endogenous NADPH-dependent reactive oxygen species generation, then a dramatic increase in tyrosine phosphorylation was observed (major phosphotyrosyl bands at 222 kDa, 200 kDa, 159 kDa, 133 kDa, 116 kDa and 82 kDa) in concert with the functional activation of the spermatozoa. A causal association between reactive oxygen species generation, tyrosine phosphorylation and sperm function was indicated by studies with the ionophore, A23187, which induced high rates of spermoocyte fusion together with enhanced rates of reactive oxygen species production and the increased expression of phosphotyrosyl proteins. This functional response to A23187 could be abrogated, without any concomitant change in sperm motility or viability, by using membrane permeant thiols or catalase to suppress the reactive oxygen species-induced increase in phosphotyrosine expression. The fact that the biological responses of human spermatozoa to biological agonists (recombinant human ZP3 and progesterone) could also be inhibited by catalase indicated the general relevance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed1995

A 10-year analysis of case load and weighted workload in a single Health Board.

This study analysed the general surgical activity in a single Health Board in terms of caseload (case counting) and Intermediate Equivalent (IE) workload. Endoscopy and surgery performed wholly within the specialist vascular and urological units were excluded. Some 180,466 procedures were prospectively recorded through the Lothian Surgical Audit over a 10-year period (1983-92). They have now been weighted to reflect workload according to the British United Provident Association's schedule of procedures. 5,058 (2.8 percent) procedures could not be 'matched' and in a further 2,400 (1.4 percent) there was an error in the Lothian Surgical Audit code leaving 172,968 operations for analysis. The total number of operations (caseload) performed annually fell by 12 percent over the 10-year period. This fall was entirely due to a 28 percent decrease in the number of minor operations. The total annual IE weighted workload rose by 2.7 percent for the 10-year period. Analysis by IE workload revealed that the fall in minor operations had been compensated for by an increase in complex major operations (CMO). The total caseload of CMO had increased from 224 (1.0 percent) to 551 (2.9 percent). This represented an increase in the proportion of workload from 5.3 percent to 12.45 percent. Thus a 1.9 percent increase in case load represented a 7.1 percent increase in IE workload. In the final year major and complex major operations formed 24.6 percent of the caseload which represented 53.2 percent of IE weighted activity. This study suggests that IE workload based on the BUPA schedule is a valid and reproducible method of weighting that accurately reflects the changing workload of different case mixes. This differential must be appreciated to ensure accurate allocation of resources. In future surgical activity,including waiting lists,should be assessed by weighted workload rather than case numbers.

General Surgery↗
PubMed1994

Structure of the O-linked carbohydrate chains of porcine zona pellucida glycoproteins.

The N-linked carbohydrate chains of porcine zona pellucida glycoproteins were released by digestion with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F and subsequently separated from the O-glycoprotein by gel-permeation chromatography on Bio-Gel P-100. The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment. Fractionation of the extremely heterogeneous mixture of O-linked oligosaccharide alditols was achieved by a combination of chromatographic techniques comprising gel-permeation chromatography on Bio-Gel P-4 and P-6, anion-exchange FPLC on Mono Q, and high-pH anion-exchange chromatography on CarboPac PA-1. The primary structures of 32 O-glycans were determined by one- and two-dimensional 1H-NMR spectroscopy. The major part of the analyzed compounds contain a combination of the structural elements Gal beta 1-4GlcNAc beta 1-3Gal beta 1-3GalNAc-ol, Gal beta 1-4(6SO4-)GlcNAc, and alpha 2-3-linked Neu5Gc or Neu5Ac. This series of compounds has the following structure, where n = 0 to > 6: [Neu5Gc/Ac alpha2-3]0-1[Gal beta 1-4(6SO4-)GlcNAc beta 1-3]nGal beta 1-4GlcNAc beta 1-3Gal Beta 1-3GalNAc-ol. In addition, smaller compounds were identified in which the Gal beta 1-3GalNAc-ol core is substituted by Neu5Gc/Ac alpha 2-6-linked to GalNAc-ol and/or Neu5Gc/Ac alpha 2-3-linked to Gal. Furthermore, oligosaccharides were obtained in which the distribution of 6-O-sulfated GlcNAc residues differs from that in the above-mentioned general structure, and a small portion of the oligosaccharides has the GlcNAc beta 1-3GalNAc-ol core structure. Analysis of the endo-beta-galactosidase digests of pools of N- and O-glycans indicated that the two types of oligosaccharides contain qualitatively similar poly(N-acetyllactosamine) chains. In the case of the N-linked carbohydrate chains, multiple branching of the core structures occurs, resulting in an even larger heterogeneity than observed for the O-linked carbohydrate chains.

Animals↗