Search PubMed⌕ Search

Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 19 recordsLinked to original sources
PubMed2007

Goal-directed training: linking theories of treatment to clinical practice for improved functional activities in daily life.

BACKGROUND: Goal-directed training is an activity-based approach to therapy. Meaningful, client-selected goals are used to provide opportunities for problem solving and to indirectly drive the movements required to successfully meet the task demands. This is in contrast to interventions that focus on changing body functions. Here, the principles of goal-directed training will be studied through two case studies with the aim of linking theories of treatment to clinical practice. PRINCIPLES ILLUSTRATED: The approach is based on the dynamic systems motor control theory and occupation-based therapy models, which suggest that movement patterns emerge from the interaction between the person's abilities, environment and the goal. Motor learning principles are applied to structure and schedule practice. THEORY IN PRACTICE: Four components provide the basis for goal-directed training: (1) selection of a meaningful goal; (2) analysis of baseline performance; (3) intervention/ practice regime; and (4) evaluation of outcome. Two individuals with acquired brain injury practised self-care tasks: eating and tying hair into a ponytail. Intensive training was undertaken over four weeks and the intervention outcome measured using the Goal Attainment Scale. CONCLUSIONS: The positive achievements in the self-care tasks illustrated that theories of motor control and motor learning can be applied to goal-directed training. The examples demonstrated that the approach could be applied to individuals with a range of abilities.

Activities of Daily Living↗
PubMed2006

Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer.

To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2'-deoxycytidine (5-Aza-CdR) and zebularine were investigated in TCC and RCC cell lines. The methylation frequency of APAF-1 (DAPK-1) was 100% (77%) in TCC and 100% (33%) in RCC. The methylation levels of APAF-1 could differentiate between the individual tumour stages in TCC as well as in RCC. The APAF-1 methylation levels in RCC were significantly higher in tumours larger than 4 cm and in high-grade tumours. The methylation frequencies in normal tissue for APAF-1 (DAPK-1) were 11% (8%) in bladder tissue and 9% (5%) in kidney tissue. The growth-inhibitory effect of the demethylating agents in TCC (RT4, T24) and RCC (A498, ClearCa-5) cell lines resulted in a 17-132% prolongation of the doubling time (DT). In RCC cell lines, zebularine was superior to 5-Aza-CdR in achieving a DT prolongation. Quantitative real time RT-PCR detected a re-expression of mRNA transcripts of APAF-1 or DAPK-1. In conclusion, demethylating agents effectively retard growth of TCC and RCC cell lines. Methylation level analysis of specific genes has the potential for further tumour characterisation in TCC and RCC.

Aged↗
PubMed2006

Frequent epigenetic inactivation of p53 target genes in seminomatous and nonseminomatous germ cell tumors.

Hypermethylation of tumor-suppressor genes has been implicated in the pathogenesis of human cancers. This study was designed to examine the methylation profiles of a selected group of p53 target genes (APAF-1, CASP-8, DAPK-1, IGFBP-3) and to correlate the findings with the histopathological characterization of testicular germ cell tumors (TGCT). Promoter methylation status was analysed by highly sensitive real-time methylation-specific PCR in 46 primary TGCTs (26 seminomas and 20 nonseminomas) and 15 normal testicular tissue samples. APAF-1 methylation was detected in all of the seminomatous and nonseminomatous TGCTs as well as in 60% of normal testicular tissue. Methylation of DAPK-1 was frequent in seminomas (50%) and nonseminomas (20%), but not in normal testicular tissue (6%). The degree of DAPK-1 methylation correlated with the clinical stage of the disease (P=0.05) and was useful in differentiating seminomatous from nonseminomatous, and malignant from nonmalignant testicular tissue (P=0.04 and 0.02, respectively). The APAF-1 methylation index achieved a highly significant differentiation between seminomatous or nonseminomatous tissue and nonmalignant testicular tissue (P=0.0001). In testicular tumorigenesis, promoter methylation of specific p53 target genes occurs at early stage but to varying degrees. Methylation also occurs in normal testicular tissue, which is in contrast to findings in other urogenital malignancies. Further studies will be necessary to determine whether the methylation level may be used as marker for risk estimation, especially in clinical stage I disease.

Apoptosis Regulatory Proteins↗
PubMed2006

Quantitative real-time RT-PCR of CD24 mRNA in the detection of prostate cancer.

BACKGROUND: Gene expression profiling has recently shown that the mRNA for CD24 is overexpressed in prostate carcinomas (Pca) compared to benign or normal prostate epithelial tissues. Immunohistochemical studies have reported the usefulness of anti-CD24 for detecting prostate cancer over the full range of prostate specimens encountered in surgical pathology, e.g. needle biopsies, transurethral resection of prostate chips, or prostatectomies. It is a small mucin-like cell surface protein and thus promises to become at least a standard adjunctive stain for atypical prostate biopsies. We tested the usefulness of real-time RT-PCR for specific and sensitive detection of CD24 transcripts as a supplementary measure for discriminating between malignant and benign lesions in prostatic tissues. METHODS: Total RNA was isolated from snap-frozen chips in 55 cases of benign prostatic hyperplasia (BPH) and from frozen sections in 59 prostatectomy cases. The latter contain at least 50% malignant epithelia. Relative quantification of CD24 transcripts was performed on the LightCycler instrument using hybridization probes for detection and porphobilinogen deaminase transcripts (PBGD) for normalization. RESULTS: Normalized CD24 transcript levels showed an average 2.69-fold increase in 59 Pca-cases (mean 0.21) when compared to 55 cases of BPH (mean 0.08). This difference was highly significant (p < 0.0001). The method has a moderate specificity (47.3%) but a high sensitivity (86.4%) if the cutoff is set at 0.0498. CD24 expression levels among Pca cases were not statistically associated with the tumor and lymph-node stage, the grading (WHO), the surgical margins, or the Gleason score. CONCLUSION: The present study demonstrates the feasibility of quantitative CD24 RNA transcript detection in prostatic tissues even without previous laser microdissection.

Adenocarcinoma↗
PubMed2006

["Second opinion centers". Approach for improving the quality of treatment for testicular tumors].

According to estimations of the German Cancer Research Center in Heidelberg, the management of germ cell tumors in Germany is characterized by a marked difference between the actual mortality and the mortality to be expected with adequate implementation of the therapy standard. Our aim is to reduce the mortality rate by introducing a treatment procedure supported by a second opinion center.

Cancer Care Facilities↗
PubMed2006

[Therapeutic options for hormone-refractory prostate cancer].

For a long time, hormone-refractory prostate cancer was regarded as a chemoresistant tumor. The introduction of taxanes has prompted a change in this opinion. For the first time treatment with 75 mg/m(2) docetaxel every 3 weeks has evidenced a survival benefit in a phase III trial (median survival of 18.9 months versus 16.5 months with mitoxantrone). Further advantages were improved pain reduction and quality of life. Neutropenia was foremost among the side effects. Docetaxel is currently the standard treatment for hormone-refractory prostate cancer. The morbidity of metastatic hormone-refractory prostate cancer is influenced by bone metastases. Pain is a prominent feature. Skeletal complications are frequent. Therapy with 4 mg zoledronic acid reduced skeletal complications significantly in comparison to placebo. The most pronounced effect is the reduction of pathological fractures. Side effects include flu-like symptoms, muscle pain, and edemas. Zoledronic acid also belongs to the standard treatment of hormone-refractory prostate cancer with bone metastases.

Androgen Antagonists↗
PubMed2006

[Noninvasive and invasive bladder cancer: diagnostics and treatment].

Therapy of superficial bladder tumors is transurethral resection (TUR), and in cases of pT1 or high-grade tumors a re-TUR is indicated. Patients with carcinoma in situ receive intravesical chemotherapy or BCG for at least 3 months. Persistent carcinoma in situ may be treated by radical cystectomy. With the provision of a functionally adequate urinary diversion, cystectomy represents an effective treatment for patients with muscle-invasive bladder cancer without metastatic spread. Regional lymph node metastases can be found in up to 15% of stage T1 disease and are present in 33% of stage T3/4 lesions. Thus, lymphadenectomy gains diagnostic and possibly also therapeutic importance. For selected patients, who cannot be treated by radical cystectomy, multimodal concepts aiming to preserve the bladder are discussed. After or prior to cystectomy systemic chemotherapy may become necessary for some patients to positively affect the course of the disease in cases of locally advanced or metastatic lesions.

Antineoplastic Agents↗
PubMed2006

[A look beyond urology: vaginal cancer].

Primary carcinomas of the vagina are very rare. Nevertheless, they need to be included in differential diagnoses when carrying out a urological examination of the pelvic floor and the vagina in patients with micturition problems, also in younger patients: we report a case of a 35-year-old woman with a primary carcinoma of the vagina and present a review of the literature.

Adenocarcinoma↗
PubMed2006

[Interdisciplinary recommendations concerning the therapy for hormone-refractory prostatic carcinoma].

Therapy with Docetaxel for hormone-refractory prostatic carcinoma has for the first time led to an increase in the survival time. Docetaxel has become established as a standard therapy for his indication. Since hormone-refractory prostatic carcinoma is not uniformly defined and is thus for prognosis not a homogeneous entity, the prospects at the start of chemotherapy are uncertain. In the summer of 2005 these questions were addressed in an interdisciplinary consensus conference. It was agreed that the 3-week scheme with 75 mg/m (2) as standard and the indication for symptomatic patients were above question. Opinions differed with regard to the use of chemotherapy in asymptomatic patients. In addition, recommendations for the performance and monitoring of the therapy were formulated.

Antineoplastic Agents, Hormonal↗
PubMed2006

Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison's disease in Portuguese Water Dogs.

Addison's disease, an immune-mediated disorder caused by destruction of the adrenal glands, is a rare disorder of Western European populations. Studies indicate that the disorder is polygenic in nature, involving specific alleles of the CTLA-4, DRB1*04 and DQ, Cyp27B1, VDR and MIC-A and -B loci. A similar immune form of Addison's disease occurs in several breeds of domestic dog, with frequencies ranging from 1.5 to 9.0%. The high frequency of the disease in domestic dog breeds likely reflects the small number of founders associated with many breeds, subsequent inbreeding, and the frequent use of popular sires. The Portuguese Water Dog (PWD) is a significantly affected breed. An analysis of 11,384 PWDs surveyed between 1985 and 1996 suggests a breed-specific disease incidence of 1.5%. As with humans, the disease is typically of late onset. This study involves a genetic comparison of Addison's disease in the PWD to the analogous disease in humans. The study is facilitated by the existence of complete pedigrees and a relatively high degree of inbreeding among PWDs. The breed originated from 31 founders, with 10 animals responsible for 90% of the current gene pool. We describe, specifically, the identification of two disease-associated loci, on Canis familiaris (CFA) chromosomes CFA12 and 37, which are syntenic with the human DRB1 histocompatibility locus alleles HLA-DRB1*04 and DRB1*0301, and to a locus for immunosuppression syntenic with CTLA-4. Strong similarities exist therefore in the complex genetic background of Addison's disease in humans and in the PWD. With the completion of the canine and human genome sequence, the purebred dog is set to become an important comparative model for Addison's as well as other human immune disorders.

Addison Disease↗
PubMed2005

New guidelines for clinical stage I testicular seminoma?

Clinical stage I (CS I) seminoma has been the subject of various studies aimed at finding the ideal treatment. Due to its high radiosensitivity, radiotherapy has been the standard approach for decades. However, the fact that CS I seminoma has a recurrence rate of only 15-20% has prompted many suggestions for better treatment stratification offering surveillance therapy for a subgroup of patients. Moreover, carboplatinum-based monochemotherapy has been the topic of various retrospective studies demonstrating equal effectiveness for adjuvant chemotherapy with one cycle of carboplatin. Since seminoma affects men in their mid-30s, only few reports have been published on long-term survival with reference to radiotoxicity and secondary malignancies. Long-term side effects and secondary malignancies pose an increasing problem for long-term survivors of primary malignancies treated by chemo- or radiotherapy. This becomes evident after a follow-up of 15 years. Since recent studies have disclosed unexpectedly high long-term morbidity and mortality after irradiation, this article critically reviews the value of radiotherapy and carboplatinum-based chemotherapy as equally effective treatment options for CS I seminoma.

Antineoplastic Agents↗
PubMed2005

Combined research and clinical learning make Rural Summer Studentship Program a successful model.

CONTEXT: Many medical schools would like to provide students with opportunities to learn and perform practical research and to have positive rural learning experiences. Rural physicians often have research ideas, but may lack the skills or assistance to perform the research. PROGRAM DESCRIPTION: The unique Rural Summer Studentship Program (RSSP) at The University of Western Ontario (Western) places students with preceptors in small and mid-sized communities throughout Southwestern Ontario where they have an opportunity to perform rural health research, combined with clinical learning, for 8 weeks in the summer after the first or second year of medical school. Secretarial coordination, research assistant support and senior faculty supervision were provided. OUTCOMES: From 1999-2003 inclusive, 44 students have participated including eight who participated over two summers. Projects were carried out in more than 20 communities with over 30 preceptors. Already, two students have had their research published in peer-reviewed journals and six have presented at major conferences. Participating students indicated an increase in interest in rural and regional medicine and in their knowledge of rural and regional medicine and patient care. They rated the value of RSSP highly as part of their medical education, even compared with other electives/selectives. CONCLUSION: The RSSP model developed at Western provides a highly rated, successful combination of supported medical student research and clinical learning with preceptors in small and mid-sized communities.

Education, Medical, Undergraduate↗
PubMed2005

How septic is urosepsis? Clinical course of infected hydronephrosis and therapeutic strategies.

Despite rapid decompression of the upper urinary tract, some patients show signs of systemic inflammatory response syndrome (SIRS) or septic shock syndrome when infected hydronephrosis is diagnosed. Clinical and biological parameters were analyzed retrospectively in 189 patients diagnosed with hydronephrosis regarding disease severity as well as microbiological and antibiotic features. Fifty of the 189 patients had positive urine culture in the renal pelvis and were included in the study. Fifteen patients had to be placed in the intensive care unit and two patients developed severe septic signs. An initial body temperature above 38.5 degrees C (P=0.0004) and an elevated BMI (P=0.002) were the only parameters that indicated a higher risk of developing SIRS or sepsis. Typical biological parameters were not helpful in differentiating patients who will develop urosepsis. Further research is necessary to provide conclusive evidence of the value of other early prognostic markers in patients with infected hydronephrosis.

Aged↗
PubMed2005

Basal ganglia calcification and psychosis in 22q11.2 deletion syndrome.

Intracerebral calcifications are a facultative symptom of hypoparathyreoidism in 22q11.2 deletion syndrome (22qDS). We describe a patient with 22qDS, basal ganglia calcification (BGC) and psychotic symptoms and discuss the etiological connection of BGC with psychiatric symptoms. Future work needs to determine the prevalence of BGC in 22qDS and psychiatric disorders.

Adult↗
PubMed2005

[Carcinoma of the urinary bladder. Konservative oder operative Therapie bei PT1G3].

As no prospective randomised studies are available on therapy and outcome in T1G3 carcinoma of the urinary bladder, a decision on therapy can only be made on the basis of retrospective studies or with reference to the individual experience of a particular urologist. In this paper the advantages and disadvantages of primary cystectomy and of transurethral resection, both alone and in combination with BCG instillation, are discussed and compared.

BCG Vaccine↗