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P D Miller

Publications and source records attributed to P D Miller.

At least 19 recordsLinked to original sources
PubMed1997

Identification of a gene containing zinc-finger motifs based on lost expression in malignantly transformed rat ovarian surface epithelial cells.

We have used a rat model of epithelial ovarian cancer to identify a gene that shows decreased or lost expression in five of eight independently transformed rat ovarian surface epithelial cell lines compared to the normal progenitor cells. Hence, we refer to this gene as Lot1 (lost on transformation 1; GenBank accession no. U72620). The most abundant transcript of the gene is approximately 6 kb. This sequence contains a 1749-nucleotide open reading frame and, within the 3' untranslated region, 22 near-perfect 60-70-bp repeats and adenine- and uracil-rich areas. The deduced amino acid sequence from the open reading frame contains seven zinc-finger motifs of the C2H2 type, as well as proline-, glutamine-, and glutamic acid-rich areas. The gene maps to the short arm of chromosome one in the rat. Lot1 shows a limited distribution of expression in normal rat tissues, including ovary, which shows abundant expression. Furthermore, examination of DNA derived from multiple species indicates that the gene is widely conserved.

Amino Acid Sequence↗
PubMed1997

Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment.

PURPOSE: To determine the efficacy and safety of cyclical etidronate for up to 7 years in the treatment of postmenopausal osteoporosis and to examine the effects of discontinuing treatment after 2 or 5 years of therapy. PATIENTS AND METHODS: Patients were randomized at entry into the original study in 1986 to blinded treatment for 2 years with either a calcium (placebo) or an intermittent cyclical etidronate regimen, which most patients continued for a third year. Following this phase of the study, patients were enrolled into an open-label, follow-up study (years 4 and 5), during which all patients received cyclical etidronate treatment. In the present double-blind study (years 6 and 7), patients were rerandomized to receive intermittent cyclical therapy with either etidronate or placebo; all patients received calcium. The treatment regimen consisted of 400 mg/day etidronate or placebo for 14 days, followed by 76 days of elemental calcium (500 mg/day); this cycle was repeated approximately 4 times in each year. Of the 193 patients who continued in years 6 and 7 of the study, 93 were randomized to receive cyclical etidronate and 100 were randomized to receive calcium only. For purposes of efficacy analyses, patients were categorized by their total years of cumulative etidronate treatment (7, 5, 4, or 2 years). There were 51, 46, 42, and 54 patients in the 7-, 5-, 4-, and 2-year groups, respectively. Annual assessments included lumbar spine bone mineral density (BMD), as measured by densitometry, and vertebral radiographs. RESULTS: The groups receiving cyclical etidronate during this 2-year study period (7- and 4-year groups) had statistically significant mean percent increases in spinal BMD of 1.8% and 2.2%, respectively (P < 0.05) at the week 104 observation time. The 5- and 2-year groups, which did not receive etidronate during this period, had mean values of 1.4% and 0.2%, respectively (not significant) at week 104. In the 7-, 5-, 4-, and 2-year groups, the increases in spinal BMD at the end of 7 years were 7.6%, 8.6%, 8.1%, and 3.9%, respectively; these values were statistically significant for all groups compared with original baseline (year 0) (P < 0.05). BMD of the femur and wrist was maintained throughout the 7-year period. The incidence and rate of vertebral fractures were lowest in patients with the longest exposure to etidronate. Etidronate was well tolerated during the study, with low incidences of gastrointestinal side effects and nonvertebral fractures. CONCLUSIONS: Long-term cyclical etidronate is a safe, effective, and well-tolerated treatment for postmenopausal osteoporosis. Bone mass is maintained for at least 2 years after treatment with etidronate is stopped; however, further gains in spinal bone mass are seen in patients who continue therapy.

Aged↗
PubMed1997

A novel transurethral microwave thermal ablation system to treat benign prostatic hyperplasia: results of a prospective multicenter clinical trial.

PURPOSE: We evaluated the efficacy, safety and impact on quality of life of a newly designed microwave thermal ablation system in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Microwave thermal ablation was administered to 154 BPH patients at 3 centers in Canada and the United Kingdom during a single 1 to 2-hour office or clinic procedure without general or regional anesthesia and without need for potent medications necessitating intensive patient monitoring. Various measures of symptoms, voiding function and patient quality of life were assessed at baseline, 6 weeks, and-3, 6, 9 and 12 months after treatment. RESULTS: Mean American Urological Association symptom score 12 months after treatment (8.8, 95% confidence interval 7.7 to 10.0) was significantly lower (p < 0.05) by 56% than that at baseline (20.1, 95% confidence interval 19.1 to 21.0). The incidence of mild symptoms increased from 0 to 57%, while that of severe symptoms decreased from 49 to 8%. There was a significant increase (p < 0.05) in peak flow rate of 45% from 9.3 ml. per second (95% confidence interval 8.8 to 9.7) at baseline to 13.4 ml. per second (95% confidence interval 12.5 to 14.4) at 12 months. Similar symptomatic and urodynamic improvements occurred in all prostate volume categories. Convalescence was rapid after treatment with little or no need for home bed rest or restriction of usual activities. Patients expressed a high level of satisfaction with treatment and found the prostate symptoms to be significantly more tolerable. Adverse events were infrequent, transient and readily managed. CONCLUSIONS: Microwave thermal ablation proved to be safe and effective for treatment of BPH with a significant positive impact on patient quality of life.

Aged↗
PubMed1996

Isolation, characterization, and mapping to human chromosome 11q24-25 of a cDNA encoding a highly conserved putative transmembrane protein, TMC.

We report the isolation of a novel human cDNA encoding a putative transmembrane protein, TMC. The predicted protein sequence is highly conserved evolutionarily. The cDNA clone was mapped to human chromosome 11q24-25 by fluorescence in situ hybridization. mRNA expression was observed in all tissues tested with the highest levels in testes and ovary.

Amino Acid Sequence↗
PubMed1996

Identification of zinc finger mRNAs using domain-specific differential display.

An oligonucleotide primer specific for a conserved amino acid region of the Cys2/His2 zinc finger proteins was used in conjunction with mRNA differential display to amplify related mRNAs from a human ovarian cancer cell line. Six of the 12 cDNAs analyzed from the differential display polyacrylamide gel exhibited zinc finger homology at the nucleotide and predicted amino acid sequence level. None of these cDNA fragments, however, shared complete homology with genes encoding any known zinc finger proteins. All 6 cDNA fragments with zinc finger homology had a poly-A tail and 3 of these fragments contained a putative polyadenylation signal. Northern blot analysis was performed using radiolabeled probes prepared from the 12 cDNA fragments. Two of the 6 cDNA fragments with zinc finger homology hybridized to 3.6- and 6.0-kb mRNAs. In addition, 2 of the fragments which did not contain significant homology to zinc finger or any other known sequences hybridized to 4.1- and 5.8-kb mRNAs. These results suggest that domain-specific differential display may be a useful approach for the identification of novel gene family members as well as for the analysis of changes in gene expression of family members between related cell lines or tissue samples.

Amino Acid Sequence↗
PubMed1996

Consensus of an international panel on the clinical utility of bone mass measurements in the detection of low bone mass in the adult population.

Low bone mass, in the asymptomatic patient, predicts future fracture risk as well as high cholesterol or high blood pressure predicts the risk of heart disease or stroke. In patients without fractures, osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of healthy young individuals. As bone mass decreases, fracture risk increases exponentially. Prevention of the first fracture is a clinical goal. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and longterm corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatment in certain situations. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and enhance decision making.

Adult↗
PubMed1996

Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry.

Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.

Absorptiometry, Photon↗
PubMed1996

Prediction of fracture risk. I: Bone density.

Low bone mass is the most important and individually objective predictor of osteoporotic fragility fracture risk. The challenge to the clinicians who care for patients with low bone mass is to identify those who are asymptomatic and nonfractured by using a bone mass measurement technique to make a diagnosis and decide on the level of intervention. All bone mass measurement techniques have value and limitations, necessitating careful individual clinical interpretation to avoid a misdiagnosis of osteoporosis or an erroneous interpretation of serial changes in bone mass. The inverse relationship between low bone mass and increasing fracture risk needs to be carefully interpreted because this relationship has only been determined in patients with a mean age of 65 years. It is not the same in younger, perimenopausal patients. Increasing age is a strong, independent risk factor for fragility fracture. In patients older than 70 years the curves relating fracture risk to low bone mass density become exponential when more than 3.0 standard deviations below peak adult bone mass. The assessment of this relationship is a professional activity and needs clinical input from appropriately educated physicians.

Age Factors↗
PubMed1996

Comparison of simultaneous versus delayed ventriculoperitoneal shunt insertion in children undergoing myelomeningocele repair.

The timing of cerebrospinal fluid shunt insertion for those neonates with hydrocephalus in association with myelomeningocele remains controversial. To examine whether there was a difference in either the complication rate or mean hospital stay for neonates undergoing myelomeningocele repair and shunting under the same anesthetic (simultaneous group) versus those in whom shunt insertion was delayed for several days after myelomeningocele closure (sequential group), we reviewed the results obtained with these two approaches in a series of 69 consecutive patients who underwent both myelomeningocele closure and shunt insertion at our institution between 1987 and 1993. Twenty-one infants underwent simultaneous myelomeningocele repair and shunting, and 48 underwent sequential procedures. The decision to shunt concurrently with myelomeningocele repair rather than in a delayed fashion was based primarily on surgeon preference rather than initial head circumference, which did not differ significantly between the two groups. The frequency and type of hydrocephalus-related complications (e.g., wound leak, cerebrospinal fluid infection, or shunt malfunction) that occurred during the first 6 months after myelomeningocele closure were compared between the two groups. Neither the overall frequency of complications nor the frequency of cerebrospinal fluid infection, shunt malfunction, or symptomatic Chiari malformation differed significantly between the two groups. In contrast, there was a significantly higher rate of myelomeningocele wound leak in the sequential group versus the simultaneous group (eight versus zero; P = .05). Mean hospital stay for the sequential group was also significantly longer than the simultaneous group (22 days versus 13 days; P = .05). These results suggest that simultaneous myelomeningocele repair and ventriculoperitoneal shunt insertion reduces hospital stay and back wound morbidity in those patients with evidence of hydrocephalus at birth, without an inordinate increase in shunt-related complications.

Cerebrospinal Fluid Shunts↗
PubMed1996

Surgical advances in the coverage of exposed roots.

A review of the past year's literature on the coverage of exposed roots reveals that surgical advances have centered on the use of membranes for guided tissue regeneration as well as surgical ingenuity combining subepithelial connective tissue with previously described root coverage techniques. In this review, the articles are critiqued, and their clinical significance is discussed. Surgical correction of exposed roots has become a remarkably successful and predictable procedure with either connective tissue or guided tissue regeneration. In most cases, connective tissue grafting for root coverage should be preferred to guided tissue regeneration, and the use of epithelialized palatal tissue (free gingival graft) for root coverage is a dated procedure.

Connective Tissue↗
PubMed1995

Alternate strategies in lesion-induced reactive synaptogenesis: differential expression of L1 in two populations of sprouting axons.

In the CNS the cell adhesion molecule L1 plays a role in axonal growth and fasciculation. Since its roles in synapse formation and CNS regeneration are unknown, we followed the staining of L1 through the sequence of degeneration and reactive axon sprouting in the denervated outer molecular layer (ML) of the hippocampal dentate gyrus following ipsilateral entorhinal cortex (ERC) lesion. We compared immunohistological and ultrastructural localization of L1 and employed image analysis to evaluate lamina-specific changes over time. L1 staining was uniformly distributed over the ML in unlesioned animals. Following ERC lesion, L1 staining markedly declined in the outer ML; L1 staining in the inner ML remained constant. Over 30 days postlesion, commissural and associational (C/A) afferents from inner ML sprouted partway into the denervated zone, and L1 was expressed on these sprouting afferents. L1 staining exactly corresponded to fiber outgrowth as assessed by Holmes fiber stain. As the L1-bearing axons of the C/A projection expanded, staining for embryonic N-CAM (reexpressed on the dendrites of the denervated zone) appeared to recede. There was never overlap of L1 and embryonic N-CAM staining; the difference always marked the boundary between inner and outer ML. Ultrastructural analysis confirmed localization of L1 staining to axonal profiles, indicating that the new pattern of L1 staining reflected distinct types of axonal growth. These changes in cell adhesion molecule expression closely paralleled the known sequence of reactive synaptogenesis and axonal sprouting and demonstrate a link between cell adhesion molecule expression and axonal sprouting during self-repair by the CNS.

Afferent Pathways↗
PubMed1995

Hypothermia attenuates the normal increase in interleukin 1 beta RNA and nerve growth factor following traumatic brain injury in the rat.

Significant morbidity and mortality associated with traumatic brain injury (TBI) are allied with secondary posttrauma inflammatory complications. Hypothermia has been suggested as a possible treatment to lessen or suppress these inflammatory reactions. We report here that interleukin 1 beta, a cytokine responsible for initiating inflammatory cascades, is elevated in rat cortex within 6 h of TBI in the rat. Nerve growth factor (NGF) RNA and protein also increased subsequently, and NGF protein remained elevated for up to 7 days. Four hours of whole body hypothermia (32 degrees C), applied immediately after the TBI, attenuated the posttrauma increase in IL-1 beta RNA and eliminated the increase in NGF RNA and protein observed in cerebral cortex following TBI. Thus, hypothermia may be an effective therapy to diminish the posttrauma inflammatory cascade in the brain (as suggested by the decrease in IL-1 beta). However, the same treatment may hinder the brain's intrinsic repair mechanisms. Optimal treatment may, therefore, require supplemental administration of neurotrophic factors or other agents along with hypothermia.

Animals↗
PubMed1995

Teaching ethics in psychiatry: a one-day workshop for clinical students.

In this paper we describe the objectives of teaching medical ethics to undergraduates and the teaching methods used. We describe a workshop used in the University of Liverpool Department of Psychiatry, designed to enhance ethical sensitivity in psychiatry. The workshop reviews significant historical and current errors in the ethical practice of psychiatry and doctors' defence mechanisms against accepting responsibility for deficiencies in ethical practice. The workshop explores the student doctors' own group ethos in response to ethical dilemmas, and demonstrates how the individual contributes to and is responsible for the group ethos through participation and also through nonparticipation. The student feedback about the workshop is reviewed. The Toronto Ethical Sensitivity Instrument was used to assess whether or not the workshop altered sensitivity. Compared to a control group the attenders' sensitivity was significantly increased (on Student's t-test p equals or is less than 0.002).

Education, Medical, Undergraduate↗
PubMed1995

Retroviral-like sequences specifically expressed in the rat ovary detect genetic differences between normal and transformed rat ovarian surface epithelial cells.

We have identified a repetitive DNA element in the rat genome that we demonstrate to be suitable to detect molecular genetic differences between normal and malignantly transformed rat ovarian surface epithelial cells by genome scanning. With fluorescence in situ hybridization, we show that these elements are widely distributed in the rat genome, and that a member of this family is present within a homogeneously staining chromosomal region of tumorigenic rat ovarian surface epithelial cells. The homogeneously staining chromosomal region infers the presence of an amplified DNA sequence in the tumor cells, and we provide molecular evidence for an amplicon in this DNA by genome scanning using a probe related to these elements. Sequence analysis revealed that these elements have the structural features of retroviral DNA. We show that they are transcriptionally active in the rat ovary, but not in a wide range of other normal rat tissues. In situ hybridization to ovarian tissue sections revealed that the elements are expressed in granulosa and theca interna cells and in the surface epithelial cells adjacent to preovulatory follicles. Based on this property, we refer to these retroviral-like elements as ovary-specific transcribed sequences. Partial sequence analysis of multiple members of this family and the range in transcript sizes strongly suggest that multiple members of this retrovirus-like family are transcriptionally active. We speculate that binding by one or a combination of ovary-specific transcription factors to regulatory sequences within the genomic ovary-specific transcribed sequences units contributes to the tissue specificity of their expression.

Animals↗
PubMed1994

Rapid expression and transport of embryonic N-CAM in dentate gyrus following entorhinal cortex lesion: ultrastructural analysis.

Neural cell adhesion molecules are known to be important in axon guidance and synapse formation in the developing brain. The embryonic form of neural cell adhesion molecule (eN-CAM) is reexpressed in the outer molecular layer (OML) of the dentate gyrus following entorhinal cortex (ERC) lesion. Ultrastructural analysis revealed localization of eN-CAM to the membrane of granule-cell dendritic membranes and occasionally axons within the denervated zone. Because eN-CAM is expressed rapidly (within 2 days) after ERC lesion, we were interested in the temporal sequence of expression. Denervated hippocampi (12, 15, 24, and 48 hours post-ERC lesion) were stained with anti-eN-CAM and processed for immunoelectron microscopy. At 12 hours, there was no evidence of staining for eN-CAM. By 15 hours after lesion, membranes of both dendrites and axons throughout the molecular layer exhibited moderate eN-CAM staining, and dendritic cytoplasm was heavily labeled. Twenty-four hours following lesion, plasma membrane staining of eN-CAM on both axons and dendrites had increased in intensity within the OML, whereas membrane eN-CAM staining was diminished in the inner molecular layer (IML), and the intradendritic cytoplasmic staining disappeared. By 48 hours after lesion, eN-CAM staining had disappeared from the IML but remained intense and widely distributed in the OML. These findings suggest a rapid transport of de novo synthesized protein. A generalized reaction appears to occur immediately following denervation, and eN-CAM is up-regulated in the complete expanse of the dendritic membrane, despite the fact that only the OML is denervated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Upregulation of nerve growth factor following cortical trauma.

As part of the inflammatory response to brain injury, CSF and tissue levels of interleukin-1 beta (IL-1 beta) are elevated after trauma. This elevation in IL-1 beta initiates a cascade of events among which may be an upregulation in nerve growth factor (NGF) in brain tissue. We infused IL-1 beta into the ventricle of adult rats and found a two- to fourfold increase in NGF in the cerebral cortex, hippocampus, and cerebellum, suggesting that IL-1 beta induced in vivo may also increase NGF in the brain. To test this hypothesis we utilized two models of traumatic brain injury (TBI) in the rat and examined NGF protein and RNA in the cortex over a period of several days. Both weight drop and controlled cortical contusion models of CNS trauma demonstrated large and significant increases in NGF protein in the cortex. NGF RNA was assessed in the controlled cortical contusion model and increased approximately fivefold by 1 day post-trauma. The remarkable elevation of NGF observed following TBI suggests that its role in response to injury may be other than as a target-derived growth substance. We hypothesize that the elevation of NGF in trauma induces upregulation of enzymes which suppress free-radical formation after injury.

Animals↗