Brain metastases and steroid reduction after radiotherapy.
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Antineoplastic Agents, Hormonal↗
Biomedical subjects
M J Tomlinson
Publications and source records attributed to M J Tomlinson.
The split denture: a new technique for artificial saliva reservoirs in mandibular dentures.
Xerostomia is a relatively common complaint that can make the wearing of dentures very uncomfortable for affected individuals. To help overcome this problem, a number of techniques have been proposed for incorporating reservoirs, containing salivary substitutes, into dentures. These have had varying degrees of success. This paper presents a case of a patient suffering from xerostomia who was successfully treated with a new form of reservoir denture. This new split-denture technique resulted in a reservoir denture that provided good lubrication of the oral tissues, was easily cleaned by the wearer and was produced from routine denture materials. Details of its design, construction and other potential applications are also presented.
Acrylic Resins↗
Interrelationships between seminal parameters and sperm nuclear DNA damage before and after density gradient centrifugation: implications for assisted conception.
BACKGROUND: With an increase in the use of assisted reproduction technologies the requirements of the diagnostic semen analysis are constantly changing. METHODS: Spermatozoa from patients undergoing IVF were analysed by examining the conventional semen parameters and DNA/chromatin integrity, using in-situ nick translation (NT) and the Chromomycin A(3) fluorochrome, which indirectly demonstrates a decreased presence of protamine. Samples were examined before and after preparation using discontinuous density gradient centrifugation. RESULTS: Density gradient centrifugation enriched samples by improving the percentage of morphologically normal forms by 138% and sperm nuclear integrity by 450%. Sperm nuclear integrity as assessed by in-situ nick translation (NT) demonstrated a very clear relationship with sperm concentration, motility and morphology. Morphology correlated with fertilization rates of patients undergoing IVF, while NT values of the spermatozoa post-preparation were significantly lower in pregnant patients. CONCLUSIONS: We have demonstrated that along with the classical semen parameters, the assessment of nuclear integrity improves the characterization of the semen sample and may be used as a tool for allocating patients to specific assisted reproduction treatments.
Adult↗
Psoriasis and radiotherapy.
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Arthritis, Psoriatic↗
Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement.
BACKGROUND: The importance of particles generated by wear and corrosion of joint replacement prostheses has been understood primarily in the context of the local effects of particle-induced periprosthetic osteolysis and aseptic loosening. We studied dissemination of wear particles in patients with total hip and knee replacement to determine the prevalence of and the histopathological response to prosthetic wear debris in the liver, spleen, and abdominal para-aortic lymph nodes. METHODS: Postmortem specimens from twenty-nine patients and biopsy specimens from two living patients with a failed replacement were analyzed. Specimens of tissue obtained from the cadavera of fifteen patients who had not had a joint replacement served as controls. The concentration of particles and the associated tissue response were characterized with the use of light microscopy of stained histological sections. Metallic particles were identified by electron microprobe analysis. Polyethylene particles were studied with the use of oil-red-O stain and polarized light microscopy. The composition of polyethylene particles was confirmed in selected cases by Fourier transform infrared spectroscopy and hot-stage thermal analysis. Twenty-one of the patients studied post mortem had had a primary total joint replacement. Eleven of them had had a hip prosthesis for a mean of sixty-nine months (range, forty-three to 171 months), and ten had had a knee replacement for a mean of eighty-four months (range, thirty-one to 179 months). The other eight patients studied post mortem had had a hip replacement in which one or more components had loosened and had been revised. The mean time between the initial arthroplasty and the time of death was 174 months (range, forty-seven to 292 months), and the mean time between the last revision procedure and the time of death was seventy-one months (range, one to 130 months). RESULTS: Metallic wear particles in the liver or spleen were more prevalent in patients who had had a failed hip arthroplasty (seven of eight) than in patients who had had a primary hip (two of eleven) or knee replacement (two of ten). The principal source of wear particles in the majority of these patients involved secondary nonbearing surfaces rather than wear between the two primary bearing surfaces as intended. In one living patient, dissemination of titanium alloy particles from a hip prosthesis with mechanical failure was associated with a visceral granulomatous reaction and hepatosplenomegaly, which required operative and medical treatment. Metallic wear particles were detected in the paraaortic lymph nodes in 68 percent (nineteen) of the twenty-eight patients with an implant from whom lymph nodes were available for study. In 38 percent (eleven) of all twenty-nine patients with an implant who were studied post mortem, metallic particles had been further disseminated to the liver or spleen, where they were usually found within small aggregates of macrophages occurring as infiltrates without apparent pathological importance. Polyethylene particles elicited a similar response. They were identified in the paraaortic lymph nodes of 68 percent (nineteen) of the twenty-eight patients and the liver or spleen of 14 percent (four) of the twenty-nine patients. The majority of the disseminated wear particles were less than one micrometer in size. Currently available methods lack the sensitivity and specificity necessary to detect very low concentrations of submicrometer polyethylene particles and probably underestimated the prevalence of polyethylene wear debris in the liver and spleen. CONCLUSIONS: In this study, systemic distribution of metallic and polyethylene wear particles was a common finding, both in patients with a previously failed implant and in those with a primary total joint prosthesis. The prevalence of particles in the liver or spleen was greater after reconstructions with mechanical failure. (ABSTRACT TRUNCATED)
Aged↗
Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation fourier transform mass spectrometry and computational methodology.
Collision-induced dissociation of metal-cationized N-CBZ-Gly-Pro-Gly-Pro-Ala was studied by Fourier transform mass spectrometry. Lithium-, sodium-, potassium- and rubidium-cationized peptide species were generated by matrix-assisted laser desorption/ionization (MALDI) using 2,5-dihydroxybenzoic acid as matrix, together with appropriate metal salts. The experimental mass spectrometric results were interpreted with the aid of Monte Carlo conformational searches using the Amber(*) force field, together with ab initio molecular orbital calculations with Gaussian-94 for the singly lithium- and potassium-cationized peptides. It is concluded that metal coordination plays a key role in guiding the gas-phase fragmentation of the cationized peptide. In contrast to lithium and sodium, potassium and rubidium apparently do not coordinate to the C-terminal carbonyl. When the peptide is cationized with the two smaller alkali metals, losses corresponding to alanine and CBZ are observed, while the coordination of potassium and rubidium results in only CBZ loss upon dissociation.
Amino Acid Sequence↗
Magnetic resonance imaging of the whole spine in suspected malignant spinal cord compression: impact on management.
Patients with suspected malignant spinal cord compression may present with a misleading sensory level or have multiple levels of compression that are not apparent clinically or on imaging of a limited area of the spine. To estimate how often this occurs and to evaluate a policy of magnetic resonance imaging (MRI) of the whole spine for any patient with suspected cord compression, data from 127 patients who had undergone MRI scans of the whole spine were reviewed. In 85 of 127 scans, there was evidence of compression of or impingement upon the spinal cord. A sensory level was present in 47 of these 85 patients, but in 12/47 (26%) the sensory level was four or more segments below or three or more segments above the actual lesion. Multiple levels of compression or impingement were found in 33 of 85 (39%) patients; in 24 of these, more than one region (cervical/thoracic/lumbar) of the cord was involved. For 32 patients who commenced radiotherapy to a treatment volume based on clinical criteria before the MRI scan was available, the radiotherapy fields needed modification in 16 (50%) as a result of the MRI findings. The results support a policy of MRI of the whole spine in any patient with suspected malignant spinal cord compression.
Female↗
Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice.
Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10 animals per sex per species per group) to transient-free, linearly polarized 60 Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0 gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G. Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An additional group of rats and mice was exposed intermittently (1 hr on/1 hr off) to 10 G fields for the same period of time. Endpoints evaluated included morbidity, mortality, gross pathology, histopathology, body/organ weights, clinical chemistry (rats only), and hematology (rats only). All mice and all male rats survived until the end of the study. One female rat (2-G exposure group) died during Week 7 of the study; the death was not attributed to magnetic field exposure. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. There were no gross, histological, hematological, or biochemical lesions attributed to magnetic field exposure. Statistically significant increases in liver weight and liver to body weight ratio occurred in female rats of all exposure groups but only at the termination. These data suggest that, for the variables evaluated in these studies, an 8-week exposure to linear-polarized, transient-free 60 Hz magnetic fields at field intensities of up to 10 G is not associated with significant toxicity in F344/N rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase without overt toxicity in any exposed group. It is premature, however, to make any prediction concerning the possible influence of exposure to 60 Hz magnetic fields on cancer rates.
Animals↗
Prognostic indicators for intrauterine insemination (IUI): statistical model for IUI success.
A retrospective analysis of 260 completed intrauterine insemination (IUI) cycles was used in an attempt to identify significant variables predictive of treatment success. Couples received a maximum of three IUI cycles for the treatment of anovulation, cervical factors or unexplained infertility. Male factor problems were largely excluded by pretreatment screening. The overall pregnancy rate was 19.6% per completed cycle, the miscarriage rate 15.6%, the multiple pregnancy rate 23.5% and the cancellation rate 19%. Logistic regression identified four significant IUI variables [follicle number (P < 0.005), endometrial thickness (P < 0.005), duration of infertility (P < 0.01) and progressive motility (P < 0.05)] which were the most predictive of IUI success. The chance of conceiving when only one follicle was produced was only 7.6%, whereas with two follicles this chance increased to 26%. These variables were incorporated into a statistical model to allow the prediction of the chance of success in subsequent cycles. We conclude that careful patient selection criteria coupled with successful ovarian stimulation is the model for IUI success.
Adult↗
Plasma mass spectrometry as a detector for chemical speciation studies.
Inductively coupled plasma mass spectrometry (ICP-MS), when coupled with the unique separating power of various chromatographic techniques, allows the detection of various elements at ultra-trace levels. The investigation of various toxic elements of environmental concern coupling relatively recent techniques, such as supercritical fluid chromatography (SFC) and capillary zone electrophoresis (CZE), to ICP-MS, is discussed. Comparisons have been made with detection limits obtained by using the flame ionization detector. The conventional technique of liquid chromatography for the speciation of vanadium, chromium and nickel is also discussed.
Capillary Action↗
H2-blocking drugs for dyspepsia.
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Dyspepsia↗
Immunogenicity of the L10 hepatocarcinoma in strain-2 guinea pigs.
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Animals↗
Prospective study of leukocytes and leukocyte subpopulations in semen suggests they are not a cause of male infertility.
OBJECTIVE: To determine the effects of leukocytes in semen on sperm quality and the ability to achieve conception. DESIGN: A prospective analysis of 512 couples attending a regional infertility clinic. Leukocyte subsets were quantified using a monoclonal antibody-based staining procedure. In addition to basic seminal parameters (density, motility, morphology, and antisperm antibodies), reactive oxygen species and immature germ cells were also quantified in the semen of each patient. The presence or absence of a treatment-independent conception was determined 22 months after the start of the study. Semen parameters were then related to the ability to conceive. SETTING: University-based center for reproductive medicine. PARTICIPANTS: Success or failure to conceive was recorded from 512 couples. Couples were then selected to minimize the influence of any pathology of the female on outcome. A final study group of 229 couples, in which the women had regular menstrual cycles, ovulatory midluteal serum P levels of > 18 nmol/L, and patent fallopian tubes was finally selected for analysis. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Leukocyte concentration (total or individual subsets) was not associated with either reduced semen quality or conception rates. Similarly, neither reactive oxygen species or antisperm antibody (immunobead) concentration had any bearing on the outcome. Of all semen parameters measured, only the level of immature germ cells was found to be negatively associated with the rate of conception. CONCLUSION: Measurement of seminal leukocytes in routine semen analysis appears to be of little prognostic value with regard to male fertilizing potential. As reactive oxygen species and antisperm measurement were of similar predictive value, the term "immunologic male infertility" should be redefined.
Autoantibodies↗
Prognostic significance of computerized motility analysis for in vivo fertility.
OBJECTIVE: To determine the predictive value of quantitative motility characteristics produced by the Hamilton Thorn Motility (HTM) Analyzer (Hamilton Thorn Research, Beverley, MA) for in vivo conception. DESIGN: A prospective analysis of 222 couples attending a regional infertility clinic. The measurements were made on a semen sample, and the presence or absence of a treatment-independent conception up to 22 months later was determined. The semen variables were then correlated to conception. SETTING: University based center for reproductive medicine. PATIENTS, PARTICIPANTS: The presence or absence of an in vivo conception was recorded in 222 couples in whom the influence on fertility of the female partner was minimized, i.e., normal in terms of history and examination, a regular menstrual cycle, ovulatory (midluteal serum P > 18 nmol/L [5.6 ng/mL]), and the outcome of the hysterosalpingogram was normal. The median follow-up time was 13 months (range, 5 to 22 months). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: A number of variables were significantly related to time to conception. When a forward stepwise analysis was performed, the total number of spermatozoa was selected on the first step, and average path velocity was selected on the second step. No other variables were selected. The final variables consisted of the total number of spermatozoa and average path velocity. CONCLUSION: The measurement of quantitative motility and sperm number using a HTM Analyser is of clinical value.
Electronic Data Processing↗
Round cells and sperm fertilizing capacity: the presence of immature germ cells but not seminal leukocytes are associated with reduced success of in vitro fertilization.
Fifty semen samples produced for IVF by patients diagnosed as having unexplained infertility were screened for leukocytes, leukocyte subsets, and immature germ cells using a mAB-based staining procedure. Nonfertilizing ejaculates were found to contain significantly larger numbers of immature germ cells, although no significant differences in leukocyte content were observed between groups. Neither sperm density or progressive motility were significantly different between fertilizing and nonfertilizing groups. We conclude that seminal leukocytes have little if any influence on the fertilizing capacity of the spermatozoa in patients undergoing IVF for unexplained infertility, but the presence of large numbers of germinal elements is associated with reduced fertilizing capacity and may be indicative of an immature sperm population.
Fertilization in Vitro↗
The removal of morphologically abnormal sperm forms by phagocytes: a positive role for seminal leukocytes?
A preliminary investigation was undertaken further to determine the function of the leukocytic cells found in semen. We performed semen analysis and quantified leukocyte subsets using immunocytochemical staining techniques in ejaculates of 351 patients. Leukocyte profiles were examined in relation to sperm morphological data for evidence of a sperm removal/selection process. Three types of seminal phagocytic cell were found to contain spermatozoa: small polymorphonuclear leukocytes (approximately 10-12 microns), monocytes of similar size and much larger (30-40 microns) macrophages capable of engulfing multiple sperm heads. The total leukocyte count (P less than 0.01), the numbers of phagocytic cells i.e. polymorphonuclear leukocytes (P less than 0.05), monocyte/macrophages (P less than 0.01) and HLA-DR positive cells (P less than 0.01), were significantly higher in those samples with greater than 50% ideal sperm forms. Significantly fewer of these same cell types were observed in samples with greater than 50% head defects. There was no difference in the number of tail or midpiece defects between leukocytospermic (greater than 10(6)/ml) and non-leukocytospermic semen samples. Oligozoospermic samples contained significantly fewer leukocytes (P less than 0.005), although above a concentration of 5 x 10(6)/ml, the sperm number was not correlated with leukocyte number. These data, along with repeated observation of spermatozoa or sperm fragments within phagocytic cells, support the hypothesis that leukocytes have a role in the removal of abnormal spermatozoa from the ejaculate.
Alkaline Phosphatase↗
Origin of reactive oxygen species in human semen: spermatozoa or leucocytes?
Peroxidative damage induced by reactive oxygen species (ROS) has been proposed as one of the major causes of defective sperm function. In previous studies of the production of ROS in semen, the contribution of contaminating leucocytes was not assessed. We determined the levels of ROS in 60 semen samples from men attending our infertility clinic and demonstrated by performing extraction experiments with antibody-coated magnetic beads that, within this unselected population of patients, leucocytes were the major source of ROS in the low-density Percoll fraction. Of the sperm motion parameters examined using computerized semen analysis, beat-cross frequency was the only one significantly affected by the ROS in semen.
Cell Separation↗
Positive immunoselection--a method of isolating leukocytes from leukocytic reacted human cervical mucus samples.
In this brief communication we report a simple and accurate method of isolating and quantifying specific leukocytes from midcycle human cervical mucus, using monoclonal antibody-coated magnetic beads. Cervical mucus samples (pre- and postinsemination) were broken down enzymatically and incubated with a series of these beads. This method of positive immunoselection consistently retrieved representative levels of leukocytes (means = 73.8% +/- 1.59%; mean leukocyte retrieval rate +/- S.E.) from the cervical mucus samples. Significantly more leukocytes (P less than 0.0001) were isolated from the postinsemination samples, the predominant leukocyte of which was the neutrophil, which comprised 83% of the leukocyte population. These results reaffirm that a leukocytic influx is initiated across the human uterine cervix following the introduction of semen samples, the function of which is possibly phagocytic clearance of the nonfertilizing population of sperm.
Antibodies, Monoclonal↗