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Biomedical subjects

D J Lamb

Publications and source records attributed to D J Lamb.

At least 37 records · Page 2Linked to original sources
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

Germ cell transplantation: a potential treatment of severe testicular failure.

Although the process of spermatogenesis is relatively efficient and resistant to damage, male infertility can result from exposure to toxic agents such as chemotherapeutic regimes, radiation, or occupational exposures to chemicals. Other types of infertility may result from migratory defects or poor survival of primordial germ cells during development, abnormal repopulation of the tubules by spermatogonia during development, or low cellularity of the testis (hypospermatogenesis). Presently, there are no effective therapies available to treat these patients. Recent studies in animal models have demonstrated that isolated testicular germ cells collected from testes may be transplanted into sterile recipient mice to regenerate spermatogenesis. This technology will have widespread applications in efforts to manipulate the genome and produce transgenic offspring, to improve agricultural species, to enhance sperm production in endangered species, to improve our understanding of the control mechanisms regulating spermatogenesis, and to treat male infertility.

Animals↗
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↗
PubMed1999

Infection, immunisation and atherosclerosis: is there a link?

Atherosclerosis is the predominant underlying pathology responsible for coronary heart disease (CHD). It bears all the hallmarks of a chronic inflammatory disease and typical atherosclerotic lesions contain activated macrophages and T-cells. There have been several reports of possible associations between prior exposure to a number of specific micro-organisms and subsequent CHD, and prospective epidemiological studies have reported that elevated plasma levels of particular acute phase reactants (APRs) are predictors of future cardiac events. Investigators have also shown that immunisations exacerbate atherosclerosis in experimental animal models. These data raise the possibility that immunostimulation associated with natural infection by certain organisms, or vaccination, may promote atherosclerosis. A hypothesis which may explain all these findings, is that the cellular--and perhaps humoral--responses associated with immune stimulation may enhance atherogenesis.

Acute-Phase Proteins↗
PubMed1999

Fertilization after standard in vitro fertilization versus intracytoplasmic sperm injection in subfertile males using sibling oocytes.

OBJECTIVE: To compare conventional IVF with ICSI in the subfertile male population using sibling oocytes. Results from males with isolated severe teratozoospermia also are analyzed. DESIGN: Prospective experimental study. SETTING: University based IVF clinic. PATIENT(S): Group A: 18 patients with one or more abnormalities in count, motility, or morphology. Group B: 20 patients with isolated severe teratozoospermia (< or = 4% Kruger Strict Criteria). INTERVENTION(S): Ovulation induction, random allocation of sibling oocytes, and IVF or ICSI. MAIN OUTCOME MEASURE(S): Fertilization rates (fertilization per cycle, fertilization per oocytes, and fertilization per couple) and embryo quality. RESULT(S): In group A, fertilization occurred in 13 of 18 (72%) of IVF cycles and 17 of 18 (94%) of ICSI cycles. Overall, 69 of 120 (58%) oocytes fertilized after IVF, whereas 80 of 131 (61%) fertilized after ICSI. The mean (+/-SEM) percent of oocytes fertilized per couple was 44.6%+/-9.0% with IVF and 62.7%+/-5.6% with ICSI (not statistically significant). In group B, fertilization occurred in 18 of 20 (90%) cycles after IVF and 20 of 20 (100%) cycles with ICSI. Overall, 54 of 113 (48%) of the oocytes fertilized after IVF, whereas 82 of 124 (66%) fertilized with ICSI. The mean (+/-SEM) percent of oocytes fertilized per couple was 50.9%+/-7.1 % with IVF and 66.6%+/-4.7% with ICSI. No statistically significant difference in embryo quality after IVF versus ICSI was demonstrated. CONCLUSION(S): With severe teratozoospermia, ICSI results in higher fertilization rates than conventional IVF, without altering embryo quality. In our subfertile male population, there is a trend toward improved fertilization with ICSI, with less failed fertilization.

Embryo Transfer↗
PubMed1999

Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit.

New Zealand White rabbits were injected subcutaneously with either a human dose of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further half dose of BCG or saline was injected after a further 4 weeks. The animals were subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde. The integrated plasma cholesterol levels did not differ significantly between the groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal titers and the control group. BCG immunization was also associated with increased peripheral lymphocyte and monocyte activation, as evidenced by increased surface expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05), respectively. Significantly more mononuclear cells bound to the aortic endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/-0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG immunization enhances peripheral leucocyte activation, aortic monocyte recruitment and atherogenesis in the cholesterol-fed rabbit.

Animals↗
PubMed1999

Dietary copper supplementation reduces atherosclerosis in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. In the present study we have attempted to address this issue directly by investigating the effects of dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Age matched rabbits (n = 16) were fed a 0.25-1% cholesterol diet to maintain plasma cholesterol concentrations at approximately 30 mmol/l. Eight of these animals also received 0.2% copper acetate. Control animals (n = 8) received rabbit chow without supplements. After 13 weeks on the experimental diets the animals were killed. Integrated cholesterol levels were similar for the cholesterol-fed animals (31.1+/-2.5 vs. 29.9+/-1.9 mmol/l weeks; P>0.05). Although integrated plasma copper levels were higher in the animals receiving the copper supplements, these did not differ significantly (19.0+/-4.8 vs. 15.1+/-2.9 micromol/l weeks; P>0.05). Tissue concentrations of copper were higher in the copper fed animals compared to those on cholesterol alone in aortic 14.0+/-0.75 vs. 1.8+/-0.2 microg/g wet tissue; P<0.05), carotid artery (11.4+/-3.5 vs. 4.9+/-0.9 microg/g wet tissue; P<0.05), and hepatic (332.5+/-28.6 vs. 3.3+/-1.1 microg/g wet tissue; P<0.0001) samples. The concentration of copper within the carotid artery was also significantly higher than that within the aorta (7.5+/-1.8 vs. 2.4+/-0.4 microg/g wet tissue; P<0.05). In animals fed a normal rabbit chow aortic, carotid and hepatic copper concentrations were 3.7+/-0.8, 9.4+/-3.4, and 5.0+/-1.6 microg/g, respectively. These values did not differ significantly from the cholesterol-fed animals (P>0.05). Plasma concentrations of caeruloplasmin, the major copper carrying protein, were estimated as plasma ferroxidase activity and were similar for the groups (P>0.05), as were aortic superoxide dismutase activity levels (P>0.05). Copper supplementation was associated with increased mononuclear cell adhesion to the endothelium of the carotid endothelium, with 2.6+/-0.3 adherent monocytes/1000 endothelial cells in the cholesterol plus copper-fed animals compared to 1.3+/-0.3 in the cholesterol-fed group (P = 0.0006), and 0.1+/-0.1 in the control animals (P<0.002). This may reflect the higher concentrations of copper found within the carotid artery. Histology of the thoracic aorta at the level of the third and sixth intercostal arteries, showed that copper supplementation was associated with significantly smaller intimal lesions (P<0.05 and P<0.01, respectively). These data suggest that copper supplements possibly inhibit the progression of atherogenesis.

Animals↗
PubMed1999

The role of autosomal cell apoptosis regulator genes in human spermatogenesis.

Immunohistochemical analysis of the expression of the autosomal apoptosis regulator genes, BAX, bcl-2, p53, and cyclic-AMP responsive element modulator (CREM) in testis biopsies from infertile men demonstrated that BAX, bcl-2, and p53 immunoreactivity was absent irrespective of seminiferous tubule histology. In contrast, cell-specific CREM immunoreactivity in round spermatids, with complete absence of CREM in patient biopsies showing spermatocyte maturation arrest and Sertoli cell only, was evident, suggesting a possible role of autosomal genes in the regulation of apoptosis in human spermatogenesis regulation.

Adult↗
PubMed1999

Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility.

Intracytoplasmic sperm injection (ICSI) has been used in combination with testicular sperm extraction to achieve pregnancies in couples with severe male-factor infertility, yet many of the underlying genetic mechanisms remain largely unknown. To investigate nondisjunction in mitotic and meiotic germ cells, we performed three-color FISH to detect numeric chromosome aberrations in testicular tissue samples from infertile men confirmed to have impaired spermatogenesis of unknown cause. FISH was employed to determine the rate of sex-chromosome aneuploidy in germ cells. Nuclei were distinguished as haploid or diploid, respectively. The overall incidence of sex-chromosome aneuploidy in germ cells was found to be significantly higher (P<.00001) in all three abnormal histopathologic patterns (range 39.0%-43.5%) as compared with normal controls (29.1%). The relative ratio of normal to aneuploid nuclei in the diploid cells of patients with impaired spermatogenesis was approximately 1.0, a >300% decrease when compared with the 4.42 ratio detected in patients with normal spermatogenesis. These results provide direct evidence of an increased incidence of sex-chromosome aneuploidy observed in germ cells of men with severely impaired spermatogenesis who might be candidates for ICSI with sperm obtained directly from the testis. The incidence of aneuploidy was significantly greater among the diploid nuclei, which suggests that chromosome instability is a result of altered genetic control during mitotic cell division and proliferation during spermatogenesis.

Biopsy↗