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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 127 records · Page 7Linked to original sources

Husband-wife survey responses in Malawi.

Previous efforts by demographers to describe and explain spousal differences in reporting about family planning behavior have focused on individual attributes that are assumed to be related to the practice of contraception. This study extends that research by documenting spousal disagreement on a range of issues--household items, livestock, children, and spousal communication about fertility, family planning, and AIDS. Using data from a 1998 study of 585 monogamous couples in rural Malawi, the analysis identifies a systematic gender component to reporting: For many of the survey questions considered, when spouses disagree, husbands are more likely to say "yes" and wives "no." The findings are interpreted in terms of gendered strategies in the interview process.

Acquired Immunodeficiency Syndrome↗

DNA-based detection of prostate cancer in blood, urine, and ejaculates.

BACKGROUND: Methylation-specific polymerase chain reaction (MSP) targeting promoter hypermethylation of the glutathione S transferase P1 gene (GSTP1), as the most frequent DNA alteration in prostatic carcinoma, was used for the molecular detection of cell-bound and cell-free prostate tumor DNA in various human bodily fluids. MATERIALS AND METHODS: We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, nucleated blood cells, ejaculates, urines after prostate massage, and prostate tissue from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Using a viral DNA extraction kit specifically recommended for DNA isolation from urine samples, GSTP1 promoter hypermethylation in urine sediments after prostatic massage was investigated in a cohort of 29 patients with prostate cancer and 40 controls with BPH. Fluorescently labeled MSP products were analyzed on an automated gene sequencer. RESULTS: GSTP1 promoter hypermethylation was found in 90% of tumors (18 of 20), 72% of plasma or serum samples (23 of 32), 50% of ejaculates (4 of 8), and between 36% (4 of 11; normal DNA isolation kit) and 76% (22 of 29; viral kit) of exprimated urines from patients with prostate cancer. Also, MSP identified circulating tumor cells in 30% (10 out of 33) of prostate cancer patients. Except for one urine sample, GSTP1 promoter hypermethylation was not found in tissue and body fluids from patients with BPH. CONCLUSION: GSTP1 promoter methylation analysis provides a highly specific tool for DNA-based diagnosis of prostate cancer in body fluids.

Aged↗

Molecular markers in testicular germ cell tumors--objects of clinical research or close to becoming clinical tools?

The aim of this short review is to critically evaluate hitherto investigated molecular markers for testicular germ cell tumors. Molecular parameters have been clinically established as diagnostic and prognostic markers for a number of tumors; this has not yet been achieved for germ cell tumors. There are interesting prospects, however. Studies on the ribonucleoprotein telomerase, for example, have demonstrated a correlation between enzyme activity and chemotherapeutic drug sensitivity. Moreover, innovative treatment approaches target this reverse transcriptase via telomerase antisense RNA. Another potential diagnostic marker is the detection of circulating tumor cells, which correlated with an increased relapse rate in initial studies. There are also interesting possibilities for the germ-cell-tumor-specific isochromosome [i(12)p], which is helpful in the differential diagnosis of mediastinal masses. Here initial studies demonstrated a correlation between the copy number and resistance against chemotherapeutic drugs. Without prospective studies to validate data obtained thus far, neither these nor other parameters can be assessed as diagnostic and prognostic factors. Irrespective of their immediate clinical applicability, however, investigations on molecular alterations in testicular germ cell tumors will become the basis for a molecular-diagnostically oriented subclassification of tumors as well as for novel therapeutic approaches.

Chromosome Aberrations↗

Impact of chemotherapy on male fertility.

Testicular tumors and malignant lymphomas are, with increasing incidence, the most frequent malignant diseases in men between the age of 15 and 34. With the introduction of cisplatin-based polychemotherapy, cure rates rose to over 90% in patients with germ cell tumors and were comparably favorable at around 80% in those with malignant lymphomas. In view of these high cure rates, increasing clinical importance is attached to chemotherapy induced fertility disorders. One problem involved in assessing the influence of chemotherapy on fertility is the fact that the malignant disease itself strongly alters spermatogenesis. This complicates an evaluation of the effect of cytostatic therapy on fertility disorders. There are significant cytostatic- and dose-specific differences. Longterm infertility due to cytostatic therapy may be expected in more than 50% of the patients at a cumulative dose of cisplatin > 0.6 g/m(2), cyclophosphamide > 6 g/m(2), and procarbazine >/= 4 g/m(2). However, it takes up to 3 years or more for spermatogenesis to recover after the termination of chemotherapy. An individual assessment of the post-therapeutic fertility status is extremely limited, since variance of the pretherapeutic fertility status causes interindividual differences, and the numerical data mentioned above only permit a vague estimation. Before patients undergo cytostatic therapy, cryopreservation of germ cells should thus be suggested or, in some cases, testicular extraction of spermatozoa.

Adolescent↗

Hispanic cultural norms for health-seeking behaviors in the face of symptoms.

This study examines factors that contribute to the delayed use of medical care among Hispanics when chronic disease-related symptoms (warning signs) occur. As an adjunct to a larger project funded by the National Cancer Institute, this study accessed a population of primarily Hispanic, mostly male employees at public work sites in two Arizona counties. Through focus groups and a survey of employees, a model describing the factors underlying health care use was tested. Seriousness of symptoms has the most effect on visits to doctor, with more serious symptoms leading to prompter visits. Faith in God and seriousness of symptoms both are related to the search for a doctor one can trust. Also, a cluster of variables describing past bad experiences, practical barriers, and emotional avoidance are related to the desire to get advice or medical help from someone who is close; these influence the search for a trusted doctor, which in turn leads to prompter visits to doctor.

Adolescent↗

An infant reciprocal walking orthosis: engineering development.

The growing trend of prescription of reciprocal walking orthoses for children under the age of 5 years has created a requirement for a new design of orthosis in this category. In response to this new demand, a prototype orthosis for infants, incorporating a specially developed hip joint and manufactured as a rehabilitation engineering device within the provisions of the EC Medical Devices Directive, has been produced and tested. A design feature that strongly influences the efficiency of walking is the rigidity of the body brace structure. Monitoring the specific structural performance of the body brace intended for infants showed that it would equal or improve the stiffness achieved in an orthosis for adults. Additionally its strength was comparable with the adult design, which has proven to be safe and reliable in many years of routine prescription. Incorporation of the infant body brace within a complete orthosis provided a structure of more acceptable physical dimensions for these more diminutive patients. The orthosis showed no incipient sign of failure after 100,000 cycles of representative service loading equivalent to that imposed by a 20 kg (5-year-old) patient. The results of structural assessment and cyclic load testing confirm that the design of the orthosis sufficiently satisfies the statutory requirements for devices that are safe and fit for purpose to permit field trials with patients.

Biomechanical Phenomena↗

Interpreting in mental health settings: issues and concerns.

Sign language interpreters in mental health settings face extreme linguistic and cultural difficulties in interpreting basic, everyday language used in these settings. This is particularly true when deaf clients have limited English proficiency, which often requires interpreters to use expansion techniques in order to render messages successfully. To examine how diagnostics may be affected by interpretation, Brauer (1993), Montoya et al. (2001), and Steinberg, Lipton, Eckhardt, Goldstein, and Sullivan (1998) translated two widely used psychological screening instruments into American Sign Language (ASL). The Minnesota Multiphasic Personality Inventory (MMPI) and the Diagnostic Interview Schedule-IV (DIS-IV) were selected for translation, and data from the three studies are presented and discussed. Their implications in terms of the expectations and stresses placed on interpreters are described within a framework of demand and control theory. Finally, sections of the Code of Ethics of the Registry of Interpreters for the Deaf (RID) are examined relative to both the issue of confidentiality and what the interpreter's contribution should be in mental health settings.

Deafness↗

Osteoporosis and mild metabolic acidosis in the rat after orchiectomy and their prevention: should prophylactic therapy be administered to patients with androgen deprivation?

PURPOSE: To date there has been little research on the etiology and prophylaxis of osteopenia during androgen deprivation. This condition is gaining increasing attention, partially due to the considerable osteoporosis related side effects of hormone withdrawal symptoms in patients with prostate cancer. We characterized androgen deprivation and its prophylaxis. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley rats underwent laparotomy, orchiectomy or orchiectomy with subsequently treatment with calcium acetate and sodium citrate via the water supply. Postoperative observation was 19 weeks. Test parameters were weight development, testosterone, parathyroid hormone, vitamin D, osteocalcin, cross links, hydroxyproline and cyclic adenosine monophosphate as well as bone density, tensile strength, mineral content and histomorphometry. RESULTS: Animals subjected to orchiectomy had a reduction in bone mineral content and fracture energy with mild metabolic acidosis. The markers of bone metabolism were statistically unchanged, while the ratio of trabeculae-to-tissue area decreased. Animals treated with orchiectomy, calcium acetate and sodium citrate had moderately compensated metabolic alkalosis and increased bone minerals. Fracture energy was likewise normal and there was a tendency toward higher bone metabolism. CONCLUSIONS: Castration led to a reduced increase in body mass, considerable standard deviation from biochemical and histological criteria for tubular bone and, thus, an increased fracture risk. A possible cause may be reduced formation and unchanged bone loss combined with mild metabolic acidosis. Calcium and alkalization seem to be effective prophylaxis for androgen deprivation. Considering the large number of osteoporotic complications after androgen deprivation, further clinical studies are justified to show the benefits of prophylactic therapy.

Acetates↗

Non-linear computer simulation of brain deformation.

This paper presents realistic computer simulation of deformation of the brain subject to in-vivo indentation. The work presented provides a step towards neurosurgical simulation, with applications to non-rigid registration, virtual reality training and operation planning systems and robotic devices to perform minimally invasive brain surgery. In order to properly analyze experimental data collected in-vivo, a three-dimensional, non-linear finite element model of the brain was developed. Magnetic resonance imaging techniques were used to obtain geometric information needed for the model. The shape of the force-displacement curve obtained using the numerical solution was very similar to the experimental one. The predicted forces were about 31% lower than those recorded during the experiment. Having in mind that the coefficients in the model had been identified based on experimental data obtained in-vitro, and large variability of mechanical properties of biological tissues, such agreement can be considered as very good. By appropriately increasing material parameters describing instantaneous stiffness of the tissue one is able, without changing the structure of the model, to reproduce experimental curve almost perfectly. Numerical studies showed also, that the linear, viscoelastic model of brain tissue is not appropriate for the modeling brain tissue deformation even for moderate strains.

Animals↗

Prevalence of genotypic resistance among antiretroviral drug-naive HIV-1-infected patients in Belgium.

OBJECTIVES: To estimate the prevalence and the evolution over time (1995-1998) of genotypic resistance to antiviral drugs in antiretroviral drug-naive HIV-1-infected patients in Belgium. DESIGN: Belgian Aids Reference Laboratories provided retrospective samples and clinical data from antiretroviral drug-naive HIV-1-infected patients who visited the hospital for the first time in 1995 (n=45), 1997 (n=75) and 1998 (n=111). Genotypic resistance to the three available classes of drugs was monitored using the Line Probe Assay (Innogenetics, Gent, Belgium). Additionally, ARMS-151 was performed for scoring multinucleoside resistance. RESULTS: The prevalence of genotypic resistance at baseline to nucleoside analogue reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were each between 10% and 20% for 1995, 1997 and 1998 without an increasing trend over time. For NRTIs, resistance mutations were mainly related to zidovudine in 1995, whereas in 1997 and 1998 baseline resistance was scored for zidovudine, lamivudine or for both drugs simultaneously. No patients displayed the multi-nucleoside resistance Q151M mutation. Baseline resistance mutations to protease inhibitors (PIs) did not rise significantly: 4.4% in 1995, 8% in 1997 and 9.9% in 1998. When scoring any resistance-related mutation, 26.6% displayed genotypic baseline resistance in 1995, 26.6% in 1997 and 31.5% in 1998. DISCUSSION: The prevalence of genotypic baseline resistance to any drug, as scored with LiPA, in naive HIV-1 patients in Belgium is 29%, with baseline resistance mutations to one or several drugs from all available classes of antiviral drugs. The ability of LiPA to pick up minor variants could be an explanation for the higher overall prevalence we observe, when compared to recent estimates in other countries of 16.3% and 22%, which were based on sequencing methods. According to the European guidelines for resistance testing, resistance testing in Belgium before starting antiviral therapy should be considered.

Acquired Immunodeficiency Syndrome↗

Increased incidence of luteinizing hormone-releasing hormone receptor gene messenger RNA expression in hormone-refractory human prostate cancers.

There are few options for treating hormone-refractory prostate cancer (PC). Various studies indicate that luteinizing hormone-releasing hormone (LHRH) agonists may have a direct inhibitory effect on prostate tumors mediated by specific LHRH receptors. One study evaluated LHRH receptors in hormone-dependent PC tissue, but no data have thus far been obtained on the presence of LHRH receptors in benign prostatic hyperplasia (BPH) and especially hormone-refractory PC in patients. Thus, it is not yet clear whether LHRH receptors indicate tumor-related differentiation or even hormone-refractory dedifferentiation or are likewise associated with BPH. The aim of this study was to determine the rate of LHRH receptor mRNA expression in BPH and in primary, potentially androgen-dependent and in hormone-refractory PC with clinical progression. Multiplex reverse transcription-PCR was used to simultaneously detect the expression of mRNA for LHRH receptors and beta-actin in 48 patients with BPH, 14 with a primary, possibly hormone-dependent, prostate carcinoma (PPC), and 18 with a hormone-refractory prostate carcinoma (HRPC). Sixteen of 18 samples with HRPC showed intact RNA and expressed mRNA for LHRH receptors (100%). However, the RNA-intact PPC and BPH showed significantly lower expression of mRNA for LHRH receptors (46.2 and 55.3%, respectively; variance analysis: P = 0.0017). The significantly higher expression of mRNA for LHRH receptors in HRPC indicates that therapeutic concepts should be developed that target this site of action. In addition to possible direct effects of LHRH agonists or antagonists demonstrated previously in vitro, it seems useful to apply targeted cytotoxic LHRH analogues or monoclonal antibodies.

Aged↗

Erectile function after anterior urethroplasty.

PURPOSE: We ascertained the impact of anterior urethroplasty on male sexual function. MATERIALS AND METHODS: A validated questionnaire was mailed to 200 men who underwent anterior urethroplasty to evaluate postoperative sexual function. Questions addressed the change in erect penile length and angle, patient satisfaction with erection, preoperative and postoperative coital frequency, and change in erection noted by the sexual partner. Results were stratified by the urethral reconstruction method, namely anastomosis, buccal mucosal graft, penile flap and all others, and compared with those in a similar group of men who underwent circumcision only. RESULTS: Of the 200 men who underwent urethroplasty 152 who were 17 to 83 years old (mean age 45.7) completed the questionnaire. Average followup was 36 months (range 3 to 149). Overall there was a similar incidence of sexual problems after urethroplasty and circumcision. Penile skin flap urethroplasty was associated with a slightly higher incidence of impaired sexual function than other procedures (p >0.05). Men with a longer stricture were most likely to report major changes in erectile function and penile length (p <0.05) but improvement was evident with time in 61.8%. CONCLUSIONS: Overall anterior urethral reconstruction appears no more likely to cause long-term postoperative sexual dysfunction than circumcision. Men with a long stricture may be at increased risk for transient erectile changes.

Adult↗

Quantification of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA in testicular tissue of infertile patients.

AIM: To evaluate the quantitative detection of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presenting with non-obstructive azoospermia. METHODS: hTR and hTERT mRNA expression were quantified in 38 cryopreserved testicular tissue specimens by fluorescence real-time reverse transcription-polymerase chain reaction (RT-PCR) in a LightCycler(r). This was paralleled by conventional histological workup in all tissue specimens and additional semithin sectioning preparation in cases with maturation arrest (n = 12) and Sertoli-cell-only syndrome (n = 12). RESULTS: The average normalized hTERT expression (N(hTERT)) was 131.9 +/- 48.0 copies (mean +/- SD) in tissue specimens with full spermatogenesis, N(hTERT) = 51.2 +/- 17.2 copies in those with maturation arrest and N(hTERT) = 2.7 +/- 2.4 copies in those with Sertoli-cell-only syndrome (SCOS). The discriminant analysis showed that detection of N(hTERT) (N(hTR)) had a predictive value of 86.8% (55.3%) for correct classification in one of the three histological subgroups. CONCLUSION: Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue enables a molecular-diagnostic classification of gametogenesis. Quantitative detection of hTERT in testicular biopsies is thus well suited for supplementing the histopathological evaluation.

DNA-Binding Proteins↗

Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa.

BACKGROUND: Anorexia nervosa is highly prevalent among young women. OBJECTIVE: To determine prevalence and predictive factors for regional bone loss. DESIGN: Prospective cohort analysis. SETTING: University hospital. PATIENTS: 130 women with anorexia nervosa. MEASUREMENTS: Dual-energy x-ray absorptiometry. RESULTS: The prevalence of osteopenia (-1.0 SD >/= T-score > -2.5 SD) and osteoporosis (T-score </= -2.5 SD) was 50% and 13% for the anterior-posterior spine, 57% and 24% for the lateral spine, and 47% and 16% for the total hip, respectively. Bone mineral density (BMD) was reduced by at least 1.0 SD at one or more skeletal sites in 92% of patients and by at least 2.5 SD in 38% of patients. Weight was the most consistent predictor of BMD at all skeletal sites. Twenty-three percent of patients were current estrogen users, and 58% were previous estrogen users. Bone mineral density did not differ by history of estrogen use at any site. CONCLUSIONS: Bone mineral density is reduced at several skeletal sites in most women with anorexia nervosa. Weight, but not estrogen use, is a significant predictor of BMD in this population at all skeletal sites.

Absorptiometry, Photon↗

Inhibitors of src tyrosine kinase: the preparation and structure-activity relationship of 4-anilino-3-cyanoquinolines and 4-anilinoquinazolines.

Src is a nonreceptor tyrosine kinase involved in signaling pathways that control proliferation, migration, and angiogenesis. Increased Src expression and activity are associated with an increase in tumor malignancy and poor prognosis. Several quinolines and quinazolines were identified as potent and selective inhibitors of Src kinase activity.

Enzyme Inhibitors↗

Fluorescent methylation-specific polymerase chain reaction for DNA-based detection of prostate cancer in bodily fluids.

Promoter hypermethylation of the glutathione S-transferase P1 gene (GSTP1) is the most frequent DNA alteration in prostatic carcinoma. Because this epigenetic DNA alteration can be reliably detected by methylation-specific PCR (MSP), we applied this new technique for molecular detection of prostate cancer in various human bodily fluids. We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, ejaculate, and urine after prostate massage and from prostate carcinoma tissues from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Fluorescently labeled MSP products were analyzed on an automated gene sequencer. Whereas GSTP1 promoter hypermethylation was not detectable by MSP in prostate tissue and bodily fluids from patients with BPH, we found it in 94% of tumors (16 of 17), 72% of plasma or serum samples (23 of 32), 50% of ejaculate (4 of 8) and 36% of urine (4 of 11) from patients with prostate cancer. Additionally, MSP identified circulating tumor cells in 30% (10 of 33) of prostate cancer patients. Analysis of GSTP1 promoter hypermethylation by MSP thus provides a specific tool for molecular diagnosis of prostate cancer in bodily fluids.

Adenocarcinoma↗

Direct evidence for the breakdown of the N = 8 shell closure in 12Be

Partial cross sections and corresponding momentum distributions have been studied in the one-neutron knockout reaction ( 12Be,11Be+gamma) on a 9Be target at 78 MeV/nucleon. The resulting spectroscopic factors for the only two bound states of 11Be are 0.42+/-0.06 ( 1/2(+)) and 0.37+/-0.06 ( 1/2(-)), where the errors are experimental only. This result shows that N = 8 is not a good closed shell in the neutron-rich 12Be and that the last neutron pair is two-thirds in the ( 1s(2)+0d(2)) intruder configuration.

Journal Article↗