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Biomedical subjects

D J Lamb

Publications and source records attributed to D J Lamb.

At least 19 recordsLinked to original sources
PubMed2001

Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility.

OBJECTIVE: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. DESIGN: Case-control study of two ethnic groups. SETTING: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. PARTICIPANT(S): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. MAIN OUTCOME MEASURE(S): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. RESULT(S): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. CONCLUSION(S): Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Biopsy↗
PubMed2001

Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection.

OBJECTIVE: To determine the incidence of nondisjunction for chromosomes X, Y, and 18 using fluorescence in situ hybridization (FISH) on morphologically normal sperm from infertile men who are candidates for ICSI. DESIGN: After standard hematoxylin staining, sperm with normal morphology were identified using Kruger's strict morphology criteria. The location of each normal-appearing sperm was recorded using an electronic microstage locator. Slides were subsequently subjected to FISH for detection of chromosomes X, Y, and 18 (control probe). Nuclei were relocated and analyzed under the fluorescent microscope. SETTING: University-affiliated IVF and intracytoplasmic sperm injection program. PATIENT(S): Men classified as infertile on the basis of abnormal strict morphology (<4% by Kruger's criteria). For controls, normal fertile men (n=6) were also analyzed. INTERVENTION(S): Semen smears were obtained retrospectively from infertile (n=8) and fertile (n=6) men. MAIN OUTCOME MEASURE(S): Ploidy of each cell was determined according to the number of signals detected for each probe. RESULT(S): Approximately 100-150 morphologically normal sperm were identified and located in each case. Subsequent FISH analysis of these normal sperm showed aneuploidy to range from 1.8% to 5.5% in the infertile group as compared with 0 to 2.6% among the control fertile group. Statistically significant differences in the incidence of aneuploidy for the sex chromosomes as well as for all three (X, Y, and 18) chromosomes was observed. CONCLUSION(S): Although 95% to 98% of the sperm were found to be normal for X, Y, and 18, our findings show that infertile couples undergoing ICSI are likely to be at an increased risk for having a genetically abnormal conceptus as compared with the fertile controls. These results demonstrate that normal morphology is not an absolute indicator for the selection of genetically normal sperm. Hence, observed pregnancy failures among ICSI patients may in part be due to the selection of aneuploid sperm.

Adult↗
PubMed2001

Modification of natural and artificial polymer colloids by "topology-controlled" emulsion polymerization.

A diffuse layer of water-soluble polymer chemically grafted to the surface of a hydrophobic polymer colloid has been created by the second-stage polymerization of dimethylaminoethyl methacrylate (DMAEMA) onto the biomacromolecule polyisoprene in natural rubber latex and also onto synthetic polybutadiene and polystyrene latexes. To control the locus of radical formation, the process was initiated by a redox couple wherein one component (e.g., cumene hydroperoxide) is hydrophobic and the other (e.g., tetraethylenepentamine) is hydrophilic. The modified latexes displayed a dramatic increase in colloidal stability at low pH which is attributed to grafted hydrophilic polymer acting as an electrosteric stabilizer; the effect is particularly remarkable in natural rubber latex, which usually has poor colloidal stability for pH less, similar 8. (13)C NMR was performed to verify the existence of the grafted copolymer and to quantify yield. The mechanism by which such a novel morphology can be generated is postulated to be via a process of radical formation at the particle surface followed by the subsequent grafting to the hydrophobic polymer backbone and polymerization of hydrophilic monomer in the aqueous phase. This technique is potentially useful for creating novel materials from natural rubber latex.

Butadienes↗
PubMed2001

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.

Animals↗
PubMed2001

Defects of dental appearance assessed by patient and dental student groups.

A study was carried out to establish the relative need for treatment of a range of defects of dental appearance and identify differences between individual and group assessments. Three groups (n = 42), two of patients (one referred for a defect of dental appearance and one not) and one of dental students, assessed urgency of need on a visual analogue scale (VAS), of four cases of dental defect presented as colour prints. All groups rated the need for treatment of the four cases in the same order. Data sets were non-normal with wide ranges. Patients without a defect of appearance usually assessed treatment need as significantly less urgent. Marked variation was discovered between individual assessments within otherwise similar groups. Based on group decisions, guidelines for treatment of defects of dental appearance could be established. However, so extreme are individual variations that very sympathetic application would be needed if dissatisfaction is not to result.

Adolescent↗
PubMed2001

Genetic effects of intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) must be proved safe as well as efficacious. In this communication we first review available data following ICSI pregnancies concerning frequency of spontaneous abortion, malformations, and chromosomal abnormalities. In ICSI the spontaneous abortion rate is slightly increased, just as it is in in vitro fertilization (IVF) without ICSI. Among 6077 ICSI cycles begun in 1997 in the United States, there were 17.5% pregnancy losses. The same cohort showed a malformation rate of 1.7% in live-born infants. Malformations in live-born infants are not increased: 1.7% in the United States and 2.3% in Brussels. However, the Swedish IVF Registry encompassing 1139 ICSI infants found hypospadias to be increased (relative risk 2.9, 95% C.I. 1.4 to 5.4). Birth weight and prematurity rate in ICSI pregnancies seem similar to that following conventional IVF without ICSI. The category of genetic defects for which concerns have most often been raised is chromosomal abnormalities. A cohort of 1987 pregnancies in Brussels yielded a frequency of de novo autosomal rearrangements of 0.36% and a de novo sex chromosomal abnormalities of 0.83%. Both rates are higher than expected in the general population. Various explanations for these increased cytogenetic autosomal abnormalities are explored in this communication. In addition to arising from the procedure per se, a genetic or cytogenetic abnormality in offspring of an ICSI pregnancy could arise as result of offspring inheriting the mutant gene or chromosomal abnormality conferring paternal infertility: Y deletions (DAZ) in oligospermia males, cystic fibrosis in offspring of males with congenital bilateral absence vas deferens (CBAVD), and sex chromosomal abnormalities in offspring of Klinefelter syndrome (47,XXY) males.

Abortion, Spontaneous↗
PubMed2001

Endogenous neutralizing antibodies against platelet-derived growth factor-aa inhibit atherogenesis in the cholesterol-fed rabbit.

Previous studies have shown that the B chain of platelet-derived growth factor (PDGF) has an important role in atherogenesis. In this study we have investigated the contribution of PDGF-A chain in cholesterol-induced atherogenesis in the New Zealand White rabbit. High titers of antibodies to PDGF-AA or to platelet cytosolic protein (PCP) were induced in these animals by immunization against recombinant human PDGF-AA or human PCP. Rabbits were then fed a 0.25% to 1% cholesterol-containing diet for 10 weeks to induce atherosclerotic lesions; the rabbits were then humanely killed and perfusion-fixed and their aortas were removed. The extent of atherosclerosis in the thoracic aortas was determined by quantitative morphometry after staining with oil red O. The intimal and medial areas in histological sections taken at the level of the first intercostal branch were quantified by image analysis. Immunization against PDGF-AA and PCP, but not against adjuvant alone, resulted in rising titers of antibodies within 2 weeks, the levels of which reached a plateau by 8 weeks. The antibodies to PDGF-AA were isoform-specific, recognized both human and rabbit PDGF-AA, and neutralized the biological activity of PDGF-AA in vitro. Integrated plasma cholesterol levels were similar in both groups. Compared with nonimmune rabbits (n=10), animals immunized against PDGF-AA (n=10) or PCP (n=10) had significantly smaller areas of the aorta covered by atherosclerotic lesions (24.6+/-5.1% and 18.7+/-4.2%, respectively, vs 34.4+/-4.3%; P<0.05). This was associated with a reduced aortic intimal-medial area ratio in PDGF-AA-immunized (0.009+/-0.006) and PCP-immunized (0.025+/-0.017) rabbits than in nonimmune animals (0.159+/-0.066; P<0.05). These data suggest that PDGF-AA is actively involved in cholesterol-induced atherosclerosis in the rabbit.

Animals↗
PubMed2001

The effect of powder/liquid mixing ratio on the stiffness and impact strength of autopolymerising dental acrylic resins.

The stiffness of representative cured autopolymerising dental acrylic resins was determined by calculation of a secant modulus from measurements in tension of load and extension, and related to the powder/liquid mixing ratio. The impact strengths of autopolymerising, heat-cure and commercial resins were compared. It was found that while the stiffness of autopolymerising resins was unaffected by variations in powder/liquid mixing ratio, extension to failure was greater with lower powder/liquid ratios. The impact strength of autopolymerising resins was found to be greater than that of heat-cure resins, and a tentative explanation is offered. These findings may help to explain the pattern of failure of acrylic resin denture bases.

Acrylic Resins↗
PubMed2000

Androgen receptor mutations in prostate cancer.

We analyzed the frequency and relevance of mutations in the coding region of the androgen receptor (AR) in genomic DNA extracted from 137 specimens of prostate cancer. The specimens were obtained from the primary tumors of patients affected by stage B disease [15 nonmicrodissected (group 1A) and 84 microdissected (group 1B)] and from the metastatic deposits of individuals with stage D1 disease [8 nonmicrodissected (group 2A) and 30 microdissected (group 2B)] who had not undergone androgen ablation therapy. The study was conducted by PCR-single strand conformational polymorphism (SSCP) analysis of exons 2-8 in the four groups and direct sequence analysis of exon 1 in group 1B. As positive and negative controls, we used genomic DNA extracted from genital skin fibroblasts of patients affected by various forms of androgen resistance with known mutations in the AR. To control for genetic instability, PCR-SSCP analysis of exon 2 of the human progesterone receptor was carried out on each specimen. The overall number of mutations detected was 11 (8%). No mutations were detected in any of the 99 patients with stage B disease. Eleven mutations were detected in exons 2-8 in 8 of the 38 patients with stage D1 disease (all in group 2B). Simultaneous analysis of exon 2 of the progesterone receptor was carried out, and no SSCP changes were identified. These data suggest that AR mutations are rare and presumably do not play a role in the initial phase of prostatic carcinogenesis. The presence of a significant number of AR mutations in metastatic disease indicates that mutations of this molecule may play a role in the most advanced phases of the natural history of this disease, either by facilitating growth or acquisition of the metastatic phenotype.

Humans↗
PubMed2000

Human sperm microinjection into hamster oocytes: a new tool for training and evaluation of the technical proficiency of intracytoplasmic sperm injection.

OBJECTIVE: To design a system for teaching intracytoplasmic sperm injection (ICSI) and to provide a standardized method to assess technical competency. SETTING: University andrology laboratory. DESIGN: Prospective study of method for training ICSI and prediction of ICSI outcome. PATIENT(S): Male infertility candidates for ICSI and fertile donors. INTERVENTION(S): Sperm from 14 fertile donors and 21 oligospermic patients were microinjected into hamster ova. Sperm head decondensation rates (SHD) and oocyte damage rates were measured. Hamster ICSI (HICSI) was used to train technicians, to assess competency, for quality control, and to predict ICSI fertilization. Sperm fertilization potential measured by HICSI was compared with the outcome of ICSI. MAIN OUTCOME MEASURE(S): Sperm head decondensation or fertilization. RESULT(S): Sperm head decondensation was observed in 425 of 773 hamster oocytes with a mean (+/- SD) rate of 60.9 +/- 15.5. Consistency was shown by repetitive testing of the same donor, comparing fresh and frozen semen, and testing of the multiple frozen aliquots of the same ejaculate. Technicians have been trained with this protocol. Excellent initial ICSI success rates for new technicians were demonstrated. Oligospermic semen samples (21 men, 251 hamster ova) tested in the HICSI test exhibited SHD rates from 12% to 100%. The poor outcome of ICSI in clinical cases was predicted by HICSI. CONCLUSION(S): The HICSI provides a method for determining the competency for the ICSI technician and interlaboratory comparison, for the prediction of success of sperm for ICSI.

Analysis of Variance↗
PubMed2000

Do better qualified dentists make fewer hospital referrals?

OBJECTIVE: To assess the influence of further qualifications and length of clinical experience on the number of referrals of complete denture problems made by GDPs to secondary care. DESIGN: An audit was made of complete denture referrals to Sheffield Dental Hospital between January 1997 and June 1999. METHOD: All complete denture referrals (n=257), either single complete denture or 2 complete dentures, made by locally practising NHS registered dentists (n=211) to Sheffield Dental Hospital, were recorded, along with the year of qualification and any additional clinical qualifications of referring practitioner. RESULTS: Fewer referrals were made by better qualified dentists (p=0.003). Better qualified dentists also appeared willing to treat more difficult cases. In the absence of a further clinical qualification, length of clinical experience had no effect on the number of referrals made. CONCLUSIONS: Better qualified dentists make fewer complete denture referrals, emphasising the importance of continuing education in reducing referral rates and improving patient service.

Clinical Competence↗
PubMed2000

The effect of sildenafil on human sperm motion and function from normal and infertile men.

The aim of this report was to study the effect of sildenafil, a specific type-5 phosphodiesterase inhibitor, on human sperm motility, viability, membrane integrity and sperm penetration assay. Spermatozoa were obtained from normal donors (n = 6) and infertile men (n = 6) were washed using a single Percoll (80%) gradient, suspended in Ham's F-10 medium, and incubated with various doses of sildenafil (125, 250 and 750 ng/ml); pentoxifylline (3 mM) was used as a positive control, and Ham's F-10 was used as a reagent control. Sperm motility, grade, viability, membrane integrity (by hypo-osmotic swelling test), and motion evaluation were carried out at various time intervals. Hamster ova sperm penetration assay (SPA) was used to evaluate overall sperm function. Sildenafil did not affect sperm motility, viability or membrane integrity under these conditions as compared to our Ham's control (P> 0.05). Incubation with pentoxifylline significantly enhanced sperm motility (P < 0.05) and viability without affecting membrane integrity (P < 0.05). Sperm incubated with sildenafil and pentoxifylline from both normal donors and infertile patients demonstrated no significant change in sperm penetration assay from respective controls. In conclusion, sildenafil, at the doses evaluated, did not significantly alter the motility, viability, membrane integrity or sperm penetration characteristics of human spermatozoa from normal donors and infertile patients.

Animals↗
PubMed2000

Evidence for oxidised low density lipoprotein in synovial fluid from rheumatoid arthritis patients.

The oxidative modification of human LDL has been implicated in atherosclerosis, but the mechanisms by which such modification occurs in vivo are not fully understood. In the present study, we have isolated LDL from knee-joint synovial fluid of patients with rheumatoid arthritis. We demonstrate that such LDL is oxidatively modified as evidenced by an increased negative charge, distorted particulate nature and more rapid degradation by cultured macrophages. These results indicate that formation of oxidised LDL is associated with the local inflammatory response. Because the cellular interactions in rheumatoid arthritis have analogies with those in atherogenesis, we suggest that the rheumatoid joint is a useful model of atherosclerosis in which the in vivo process of LDL oxidation may be readily studied.

Arthritis, Rheumatoid↗
PubMed2000

Male infertility: recent advances and a look towards the future.

The past decade has witnessed clinical and basic scientific advances that have revolutionized the diagnosis and treatment of the infertile male. Advances in the clinic and laboratory have resulted in men who were previously thought to be hopelessly infertile, but who are now able to conceive their own biologic offspring. In the future, we believe that the laboratory will continue to play a key role in advancing our ability both to diagnose and to treat the infertile male. We summarize here some of the major advances of the past decade that have influenced our treatment and our understanding of the etiology of male infertility. When possible, clinical innovations and advances in basic science are discussed in combination in order to emphasize the translational importance of reproductive research.

Forecasting↗
PubMed2000

Testis biopsy findings in the spinal cord injured patient.

PURPOSE: Azoospermia after electroejaculation in spinal cord injured men may be due to testicular failure or obstruction. These men can initiate pregnancy with assisted reproductive techniques, such as intracytoplasmic sperm injection, but only if sperm are present in the testis biopsy. We analyzed the histopathology of testis biopsies from spinal cord injured men and assessed whether patient factors were predictive of testis biopsy pathology. MATERIALS AND METHODS: A total of 50 paraplegic men undergoing testis biopsy were divided into 2 groups based on normal or abnormal testis histopathology. Patient age, post-injury years, level of lesion, hormonal status and semen analysis results were compared. RESULTS: Spermatogenesis was normal in 28 of the 50 patients. Hypospermatogenesis was exhibited in 15, maturation arrest at the spermatid stage in 6 and maturation arrest at the spermatocyte stage in 1 of the 22 abnormal cases. Nevertheless, mature sperm were identified in 43 of 50 biopsies (normal spermatogenesis and hypospermatogenesis). Men with normal spermatogenesis had better forward progression of sperm and a higher testosterone-to-luteinizing hormone ratio. Otherwise, there was no statistically significant correlation between study variables and testis biopsy results. No factors were predictive of testis biopsy histopathology. CONCLUSIONS: The documentation of mature sperm in 43 of 50 biopsies from spinal cord injured patients suggests that a high rate of sperm retrieval is possible using testicular sperm extraction if sperm cannot be retrieved from the ejaculate. With intracytoplasmic sperm injection techniques the majority of spinal cord injured men retain fertility potential, even if azoospermic following electroejaculation.

Adult↗
PubMed2000

Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection.

PURPOSE: We tested the hypothesis that spinal cord injury and/or anejaculation affects the outcome of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: From November 1993 to October 1998 we obtained and prospectively reviewed data on 34 ICSI cycles using electroejaculated sperm, 620 male factor infertility ICSI cycles using normal ejaculated sperm and 120 cases of obstructive azoospermia, in which microsurgical epididymal aspiration and testicular sperm extraction-ICSI were done in 93 and 27, respectively. RESULTS: A total of 34 ICSI cycles were performed in 17 couples with male infertility due to anejaculation secondary to spinal cord injury in 10 patients and retroperitoneal lymph node dissection in 5, and idiopathic in 2. In all 17 couples at least 3 previous intrauterine insemination cycles had failed. After electroejaculation 11 men had oligozoospermia and 6 normal sperm density. Median sperm retrieval volume plus or minus standard deviation was 1.9 +/- 1.9 ml., median sperm concentration 70.7 +/- 60.2 x 106 sperm per ml., median motility 10.7% +/- 10.8% and median forward progression 2.3 +/- 0.5 (scale 1 to 4). In the anejaculation group ICSI resulted in a median fertilization of 60% +/- 28%, 15% pregnancies per cycle and 29% pregnancies per couple. In the control group of 620 ICSI cycles from ejaculated specimens obtained from male patients with infertility median fertilization was 58% +/- 26%, and there were 39% pregnancies per cycle and 47% pregnancies per couple. The rate of pregnancies per embryo transfer and per couple was higher in the control than in the electroejaculation-ICSI group (p <0.05). However, there was no statistically significant difference in the fertilization rate. CONCLUSIONS: ICSI or in vitro fertilization is a viable alternative for patients with anejaculation in whom intrauterine insemination failed. While the fertilization rate is similar in these couples, the pregnancy rate is significantly lower than that achieved with ejaculated specimens from patients with severe male factor infertility. ICSI is a viable alternative for a patient with anejaculation in whom intrauterine insemination or in vitro fertilization failed.

Adult↗