Search PubMed⌕ Search

Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 55 records · Page 3Linked to original sources
PubMed2004

Best Practice No 176: Updated recommendations for HER2 testing in the UK.

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service.

Algorithms↗
PubMed2004

Why are certain premises at increased risk of equine grass sickness? A matched case-control study.

REASONS FOR PERFORMING STUDY: Equine grass sickness (EGS) occurs repeatedly on certain premises over time. Few studies have sought, or identified, the determinants of this phenomenon in order to inform advice on disease prevention strategies. HYPOTHESIS: Premises-level risk factors are important determinants of whether EGS occurs. METHODS: A matched case-control study was undertaken. Sixty premises giving rise to one or more histologically confirmed case of EGS and 120 time-matched control premises were sampled. Data were collected on pasture management, soil nutrient content, pasture nutrient content and local weather conditions for 2 weeks prior to the onset of disease. Data were analysed by conditional logistic regression. RESULTS: Multivariable modelling identified an association between EGS and increased soil nitrogen content, pasture disturbance and previous occurrence of EGS on the premises. None of the meteorological variables recorded in this study were significantly associated with EGS occurrence. No relationship between certain management practices (e.g. harrowing, fertilisation, reseeding) and the risk of EGS was detected. CONCLUSIONS AND POTENTIAL RELEVANCE: This information is useful in understanding the causal pathway of EGS and may be used in the formulation of evidence-based disease avoidance strategies.

Animal Husbandry↗
PubMed2004

Detection of germ-cell-tumor-specific gene products in peripheral blood by immunomagnetic tumor cell enrichment followed by RT-PCR.

Therapeutic procedures in patients with testicular germ cell tumors (GCT) are determined by the histopathology of the primary tumor and the tumor extension. The aim of our study was to determine whether conventional staging could be supplemented by combining enrichment of disseminated testicular GCT cells from peripheral blood with subsequent detection of germ-cell-specific gene products. Blood samples from 46 patients with GCT of different clinical stages (CS) were examined by RT-PCR before therapy and >/=8 weeks thereafter for alpha-fetoprotein, beta-human chorionic gonadotropin and germ-cell-specific alkaline phosphatase mRNA. In addition, we performed titration experiments to evaluate whether the sensitivity can be improved by previous immunomagnetic tumor cell enrichment with anti-epithelial HEA-125 microbeads. No positive results were found in controls (n=15; specificity 100%). The overall ratio of positive PCR results in the group of patients with GCTs was 28.26%. The ratio was 35.7% for CS >IIb (n=5/14 patients), 20.0% for CS IIa-b (n=4/20) and 33.3% for CS I (n=4/12). FACS analysis in titration experiments with GCT cell lines showed that previous immunomagnetic tumor cell enrichment achieved a significant increase ranging up to 185.6 times the initial ratio and thus improved the measuring conditions for detection of tumor-specific transcripts. The sole qualitative RT-PCR of tumor-specific gene products in peripheral blood is not sensitive enough to improve staging in GCT patients. Immunomagnetic enrichment of GCT cells in peripheral blood seems a promising approach for increasing the sensitivity of RT-PCR.

Calcium-Binding Proteins↗
PubMed2004

Equine grass sickness is associated with low antibody levels to Clostridium botulinum: a matched case-control study.

REASONS FOR PERFORMING STUDY: Equine grass sickness is a high mortality disease which, despite many years of investigation, is of unknown aetiology. Recent findings indicating that the disease is associated with Clostridium botulinum require support from an epidemiological study that recognises and controls for potential confounders, e.g. age, time of year and premises. HYPOTHESIS: EGS is associated with low antibody levels to C. botulinum antigens. METHODS: A matched case-control study was conducted. Data were collected from 66 histologically confirmed cases of EGS and 132 premises-matched control horses. The probability of EGS in horses was modelled using conditional logistic regression. RESULTS: EGS was significantly associated (age-adjusted P < 0.005) with low antibody levels to each of 3 clostridial antigens; C. botulinum type C and C. novyi type A surface antigens and a C. botulinum type C toxin complex toxoid. These serological risk factors for EGS remained highly significant when entered into multivariable models. This study also identified new horse-level risk factors for EGS; feeding hay or haylage was associated with a decreased risk of disease, change of feed type or quantity during the 14 days prior to disease was associated with increased risk, and the use of an ivermectin anthelmintic at both the ultimate and penultimate treatments was also associated with a significantly increased risk of EGS. CONCLUSIONS: This study provides strong support for the role of C. botulinum in the aetiology of EGS and identifies managemental risk factors for the disease. POTENTIAL RELEVANCE: Increasing anticlostridial antibody levels by vaccination and appropriate managemental interventions may decrease the risk of EGS occurring.

Animals↗
PubMed2004

Acute scrotum due to arterial bleeding mimicking non-seminomatous germ cell tumor.

Men with testicular tumors usually present with painless increase in testis size incidentally noticed by the patient. We report a case of a young patient presenting as an emergency with acute onset of massive right-sided testicular pain without previous injury. After physical examination testicular torsion could not be excluded. Ultrasound examination of the testis was suspicious for testicular tumor. Surgical exploration of the right testis by inguinal approach was performed revealing subcapsular arterial bleeding due to a small nonseminomatous germ cell tumor non-palpable on clinical examination.

Acute Disease↗
PubMed2003

Laparoscopic surgical concepts of morbid obesity.

BACKGROUND: According to the WHO, obesity and obesity with associated morbidity constitute a chronic, multi-factorial condition requiring treatment. Conservative treatment has been shown in long-term studies to be ineffective in morbid obesity. Surgical treatments break down into restrictive, malabsorptive, combined restrictive and malabsorptive or motility-reducing procedures. METHOD AND RESULTS: Laparoscopic implantation of an adjustable gastric band is an efficient restrictive measure for treating the majority of patients with this condition. The adjustable gastric band enables weight loss and food intake to be adapted to the individual patient's need. Of these patients, 80-90% can expect to lose 55-70% of their excess weight. Vertical banded gastroplasty is losing ground among the restrictive options. Preliminary experiences are encouraging, but the long-term results are disappointing when assessed by the standard criteria. Gastric bypass is gaining ground in Europe and is a standard procedure in the USA. This operation is estimated to give a 70-80% loss in excess weight, and provides a better quality of life than do restrictive procedures. The biliopancreatic diversion with duodenal switch combines a sleeve gastrectomy with a duodeno-ileal switch to achieve maximum weight loss. Consistent excess weight loss of between 70% and 80% is achieved, with acceptable decreased long-term nutritional complications. The laparoscopic approach to this procedure has successfully created a surgical technique with optimum benefit and minimal morbidity, especially in the super-obese patient. Intra-gastric stimulation is the least invasive surgical procedure at present. However, the excess weight loss is lowest with this method, at only 32% in the first 2 years after the operation. CONCLUSION: Provided that safety recommendations are observed, laparoscopic operations for obesity have a fairly low risk. The mortality rate in centres with experienced staff is less than 0.3%. The death rate due to untreated morbid obesity is significantly higher than in a comparable group of patients after surgery.

Biliopancreatic Diversion↗
PubMed2003

[Molecular diagnostics in urologic oncology. Detection of nucleic acids in urine samples].

The goal of molecular diagnostics in oncology is the early diagnosis of malignant disease processes during initial work-up or as part of follow-up. Body fluids serve as the primary material for non-invasive diagnostic methods. Besides actual tumor cells, the examination of urine can yield evidence of secreted proteins or even free nucleic acids. In principle, all of the methods available for the detection of tumor markers in tissue or blood samples can be successfully applied to the examination of urine samples. However, molecular biological examination of urine samples is associated with important problems because the cells in such samples are exposed to significant degradation and regression effects and because certain components of the urine act to inhibit the polymerase chain reaction. The present overview discusses the respective strengths and weakness of the available technology as applied to the diagnosis of urologic malignancies. Experimental studies conducted to date have reported high sensitivities and specificities for molecular diagnostics using urine samples. It is important to note that not only carcinomas of the urinary bladder can be diagnosed from material obtained in urine samples: in fact, the method can be used to diagnose entities such as renal cell and prostate carcinomas and, due to renal filtration of DNA, even non-urologic malignancies. The diagnostic application of these methods, however, remains in an experimental stage and must still clear several hurdles before becoming available for routine clinical use.

Biomarkers, Tumor↗
PubMed2003

Chromosome 18 replaced by two ring chromosomes of chromosome 18 origin.

We here describe the first example of the replacement of an autosome by two ring chromosomes originating from the missing chromosome, presented in a patient with a single chromosome 18 and two additional ring chromosomes. Detailed fluorescence in situ hybridization (FISH) analysis revealed the chromosome 18 origin of both ring chromosomes and characterized the small and the large ring chromosome as derivatives of the short and long arm of chromosome 18, respectively. The loss of subtelomeric regions of the short and the long arm of chromosome 18 in the ring chromosomes was confirmed by FISH studies. Molecular studies showed the exclusive presence of the paternal alleles for microsatellite markers located distal to the short and long arm loci D18S843 and D18S474, respectively. This indicates the maternal origin of both rings and provides evidence for substantial deletions of the distal parts of both arms of chromosome 18 in the ring chromosomes. The dysmorphic features of the patient can be explained by these deletions in both chromosome arms, as the clinical findings partly overlap with observations in 18p- and 18q-syndrome and are similar to some cases of ring chromosome 18. Centromere misdivision is suggested as one mechanism involved in the formation of the ring chromosomes.

Abnormalities, Multiple↗
PubMed2003

Hyperphosphaturia after kidney transplantation in syngeneic rats: effects on nephrocalcinosis and bone metabolism?

BACKGROUND: Studies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved. METHODS: Thirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks. RESULTS: Animals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion. CONCLUSIONS: The loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism.

Adenosine↗
PubMed2003

"Onco-tese": testicular sperm extraction in azoospermic cancer patients before chemotherapy-new guidelines?

OBJECTIVES: To examine the usefulness of pretreatment testicular sperm extraction because some patients have tumor-induced azoospermia. In view of the high cure rates for testicular germ cell tumors and malignant lymphomas, increasing clinical importance is attached to protecting fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is cryopreservation of ejaculated spermatozoa before therapy. METHODS: Contralateral testicular biopsies were taken from 14 azoospermic patients with malignant testicular germ cell tumors. In addition, 17 patients with malignant lymphomas underwent unilateral (n = 6) or bilateral (n = 11) testicular biopsy. The tissue specimens were cryopreserved, and the histologic workup was performed at the same time. RESULTS: Of the 14 patients with malignant testicular germ cell tumors, 6 had spermatozoa in their testicular biopsies. Sertoli cell-only syndrome was found in 5 patients, and 3 had maturation arrest without detection of spermatozoa. Successful sperm recovery was possible in 8 of the 17 patients with malignant lymphoma, 4 had Sertoli cell-only syndrome, and 5 had maturation arrest. None of the patients had evidence of secondary wound healing or treatment delay because of the testicular biopsy. CONCLUSIONS: Our results show that testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic cancer patients. This procedure should be considered as an option for fertility preservation in azoospermic cancer patients, because high cumulative cytostatic doses can cause irreversible fertility alterations.

Antineoplastic Agents↗
PubMed2003

Search for deletion 22q11.2 in interphase nuclei of buccal mucosa of patients ascertained by isolated cleft palate: a new diagnostic approach.

A new approach for the detection of chromosome deletion 22q11.2 in interphase nuclei from buccal mucosa cells obtained by a non-invasive procedure is described. FISH analysis has been performed on samples from a group of 101 patients that presented consecutively for speech therapy and/or surgical correction of cleft palate. A normal result has been obtained in 98 patients; a deletion 22q11.2 was present in three patients (2.8%) with cleft palate.

Adolescent↗
PubMed2003

New technical advances in swivel walkers.

Swivel walkers were commonly prescribed for children with complete thoracic lesion myelomeningocele in the 1970s and 80s, when the incidence of spina bifida in the UK was of the order of 3 per 100,000 live births. The advent of reciprocal walking orthoses provided a more suitable alternative for those with good upper limb and trunk function, and swivel walkers were then used primarily for very young or more severely disabled patients. Pre-natal screening has dramatically reduced the incidence of spina bifida in the UK and subsequently swivel walkers have been used in a wider range of pathology, including spinal muscular atrophy, multiple sclerosis, muscular dystrophy and other neurological conditions that lead to lower limb dysfunction. The detail design of these devices has been adapted to accommodate the specific problems encountered in these conditions. In particular the designs have been updated to: enable very young patients to be more readily fitted at the age of 1 year; allow the walking mechanisms to be conveniently adjusted for easier ambulation when weakness or lack of confidence inhibits performance; permit simple adjustment to a standing frame mode to enhance stability in situations of increased risk; promote manual handling practice that is compatible with the National Health Service (NHS) policy of compliance with relevant regulations. To underpin appropriate prescription and safe supply the NHS Procurement Agency have encouraged the development of a common course for all types of swivel walker.

Adolescent↗
PubMed2003

[AUO Urogenital Cancer Studies].

Quality assessment of oncological studies is mandatory. The German Cancer Society (Deutsche Krebsgesellschaft) and its affiliated organizations attained the mayer role for such purposes. The present paper demonstrates that the Association of Urological Oncoloy (AUO), which is part of the German Cancer Society, became the most widely accepted and integrative workinggroup on urogenital cancers in Germany (97 studies). The AUO does not only provide the largest public data base on urogenital cancer studies (65 items, http: www.auo-online.de) - with 18 open studies presented in the paper - but also serves as the principal driving force for interdisciplinary urogenital cancer networks and international intergroup activities (AUO/EORTC).

Clinical Trials as Topic↗
PubMed2003

The application of region-specific probes for the resolution of duplication 8p: a case report and a review of the literature.

The structural rearrangement in the short arm of a chromosome 8 in a clinically affected patient has been reinvestigated by FISH using whole chromosome painting and region specific YAC probes. An inverted duplication of the segment p22-->p11.2 and a deletion of the subtelomeric region were demonstrated. By this approach, a more detailed resolution of the duplication/deletion 8p was possible. With the application of molecular cytogenetic methods the existence of different duplication segments within the clinical entity of duplication/deficiency 8p can be shown.

Child↗
PubMed2003

Reciprocal walking orthosis with composite material body brace: initial development.

Reciprocal walking orthoses are routinely used by thoracic lesion patients for ambulation using crutches. A primary reason for their prescription is to provide therapeutic benefit and improved independence. To achieve this, maximum efficiency of walking and acceptance of the device is necessary to promote long-term compliance. Lateral rigidity in the orthosis influences walking efficiency, but the structural properties of conventional techniques for producing a sufficiently rigid body brace makes them unattractive. Currently patients and clinicians are forced to choose between greater efficiency or cosmesis of the orthosis. Composite materials have the potential to permit the required rigidity in a structure that is less obtrusive. However, their material properties could lead to unsafe forms of failure unless suitable manufacturing methods are devised. It is therefore inappropriate to supply prototypes to patients for field evaluation until laboratory investigation of innovative production methods has ensured that the orthosis is safe. A production technique has been devised that is ostensibly suitable. Prototype body braces have been tested and have been shown to have improved structural properties and safe failure modes. A test programme implemented on a complete concept orthosis has confirmed that improved lateral rigidity can be achieved with a less obtrusive body brace, and that it will behave safely for long enough to permit field evaluation.

Braces↗