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S J Miller

Publications and source records attributed to S J Miller.

At least 37 records · Page 2Linked to original sources
PubMed2001

The debate regarding continuous use of oral contraceptives.

OBJECTIVE: To determine whether oral contraceptives (OCs) can be used safely in a continuous manner to prevent monthly withdrawal bleeding. DATA SOURCES: Search of MEDLINE (1966-2000), International Pharmaceutical Abstracts (1970-2000), and the Internet. DATA SYNTHESIS: Several prospective studies have assessed the efficacy of continuous cycle OCs in preventing monthly withdrawal bleeding. Monophasic OCs are useful for this purpose. In studies using traditional OC regimens as a control, patients receiving continuously administered OCs experienced more breakthrough bleeding and spotting. Continuous use of OCs decreased headache and other menstruation-associated symptoms. No long-term trials have assessed the impact of continuous use of OCs on risk of cancer, thromboembolic disease, or fertility, concems raised by opponents of the method. CONCLUSIONS: From the data available, continuous use of OCs is an effective method for delaying withdrawal bleeding. Long-term safety data are not available.

Adult↗
PubMed2001

The sequential activation and repression of the human PDGF-B gene during chronic hypoxia reveals antagonistic roles for the depletion of oxygen and glucose.

Hypoxia and glucose deprivation, are important during many physiological and pathological processes. Cells respond to these stimuli by activating genes involved in the regulation of metabolism and angiogenesis. Platelet derived growth factor-B (PDGF-B) is involved in the regulation of angiogenesis and tumour progression and is induced by hypoxia. Most known hypoxia-induced genes are activated by the hypoxia inducible factor (HIF-1), via its binding to specific response elements. The mechanism of hypoxic induction and the effect of low glucose on PDGF-B expression have not been characterised. We show that PDGF-B exhibits a novel, biphasic regulation (induction, followed by repression below basal levels) in bladder carcinoma cells cultured under chronic hypoxia. We show that the repression observed after long-term hypoxia is due to glucose-depletion and that this can also abrogate short-term hypoxic induction. This is in contrast to the previous results showing that hypoxia/hypoglycaemia elicit the same response. We also show that a putative hypoxia response element in the PDGF-B promoter is not sufficient for hypoxic induction, although it does function as a hypoxia independent enhancer element in hepatocellular carcinoma cells.

Carcinoma, Hepatocellular↗
PubMed2001

The use of interleukins for advanced melanoma.

Treatment of metastatic melanoma using traditional chemotherapy regimens has been disappointing. However, recent work with agents that modify the host's immune system (e.g., interleukins) have provided limited but encouraging results. Interleukins are a group of molecules involved in immune cell signaling. As a high-dose, single agent therapy, Interleukin-2 (IL-2) has produced durable, complete responses in a small, but real percentage of metastatic melanoma patients, but toxicities are significant and specialized care is required. The use of IL-2 in conjunction with other chemotherapeutic and biologic agents has produced an even higher percentage of complete responses, but the trials have been relatively small to date and durability is not as well proven. IL-2 is also being tested in conjunction with vaccines, activated immune cells, and other biologic response modifiers (including IL-12). It is hoped that these will lead to further increases in the number of metastatic melanoma patients who respond in a clinically meaningful fashion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The N-terminal region of neuregulin isoforms determines the accumulation of cell surface and released neuregulin ectodomain.

Two neuregulin-1 isoforms highly expressed in the nervous system are the type III neuregulin III-beta1a and the type I neuregulin I-beta1a. The sequence of these two isoforms differs only in the region that is N-terminal of the bioactive epidermal growth factor-like domain. While the biosynthetic processing of the I-beta1a isoform has been well characterized, the processing of III-beta1a has not been reported. In this study, we compared III-beta1a and I-beta1a processing. Both III-beta1a and I-beta1a were synthesized as transmembrane proproteins that were proteolytically cleaved to produce an N-terminal fragment containing the bioactive epidermal growth factor-like domain. For I-beta1a, this product was released into the medium. However, for III-beta1a, this product was a transmembrane protein. In cultures of cells expressing III-beta1a, the amount of neuregulin at the cell surface was much greater, and the amount in the medium was much less than in cultures expressing I-beta1a. Phorbol ester treatment and truncation of the cytoplasmic tail had markedly different effects on III-beta1a and I-beta1a processing. These results demonstrate an important role for the N-terminal region in determining neuregulin biosynthetic processing and show that a major product of III-beta1a processing is a tethered ligand that may act as a cell surface signaling molecule.

Amino Acid Sequence↗
PubMed2000

Value of serum-soluble intercellular adhesion molecule-1 for the noninvasive risk assessment of transplant coronary artery disease, posttransplant ischemic events, and cardiac graft failure.

BACKGROUND: Adhesion molecules on arterial endothelium have been implicated in spontaneous atherosclerosis and transplant coronary artery disease (CAD). We studied whether elevated serum-soluble intercellular adhesion molecule-1 (sICAM-1) during the immediate posttransplant period was a risk factor for CAD, posttransplant ischemic events, or cardiac graft failure. METHODS AND RESULTS: We initially studied serum sICAM-1 in a subset of 16 cardiac allograft recipients (5.5+/-0.7 samples per patient) to determine a cutoff point that best correlated with presence of arterial and arteriolar endothelial ICAM-1 in matching endomyocardial biopsies. The cutoff value was 308 ng/mL. Subsequently, we prospectively evaluated serum sICAM-1 in serial samples (5.3+/-0.1 per patient) obtained during the first 3 months after transplantation in a validation subset of 130 recipients and correlated early sICAM-1 levels with long-term outcome. Serum sICAM-1 >308 ng/mL correlated significantly with ICAM-1 on arterial and arteriolar endothelium (P:=0.02). Cardiac allograft recipients with serum sICAM-1 >308 ng/mL had 2.67 (95% CI, 1.28 to 5.59, P:=0.009) times greater risk of CAD and 3.63 (95% CI, 1.05 to 12.5, P:=0.04) times greater risk of graft failure. Recipients with sICAM-1 >308 ng/mL also developed more severe CAD (P:=0.009) and more ischemic events (P:=0.03) after transplantation. CONCLUSIONS: Serum sICAM-1 levels can be used to noninvasively assess risk of transplant CAD, posttransplant ischemic events, and cardiac graft failure.

Coronary Artery Bypass↗
PubMed2000

A role for nuclear PTEN in neuronal differentiation.

Mutations of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a protein and lipid phosphatase, have been associated with gliomas, macrocephaly, and mental deficiencies. We have assessed PTEN's role in the nervous system and find that PTEN is expressed in mouse brain late in development, starting at approximately postnatal day 0. In adult brain, PTEN is preferentially expressed in neurons and is especially evident in Purkinje neurons, olfactory mitral neurons, and large pyramidal neurons. To analyze the function of PTEN in neuronal differentiation, we used two well established model systems-pheochromocytoma cells and cultured CNS stem cells. PTEN is expressed during neurotrophin-induced differentiation and is detected in both the nucleus and cytoplasm. Suppression of PTEN levels with antisense oligonucleotides does not block initiation of neuronal differentiation. Instead, PTEN antisense leads to death of the resulting, immature neurons, probably during neurite extension. In contrast, PTEN is not required for astrocytic differentiation. These observations indicate that PTEN acts at multiple sites in the cell, regulating the transition of differentiating neuroblasts to postmitotic neurons.

Animals↗
PubMed2000

Targeted prophylaxis with amphotericin B lipid complex in liver transplantation.

The purpose of this study is to prospectively evaluate a strategy in which prophylaxis with amphotericin B lipid complex at 3 different dosages was targeted to liver transplant recipients at high risk for the development of invasive fungal infection (IFI). High risk was defined as a postoperative requirement for prolonged (>/=5 days) intensive care unit (ICU) treatment. Consecutive high-risk patients were administered prophylaxis with amphotericin B lipid complex from day 5 after orthotopic liver transplantation (OLT) until ICU discharge or death. The first 10 eligible patients were administered 5 mg/kg/d, the next 10 patients were administered 2.5 mg/kg/d, and a final 10 patients were administered 1 mg/kg/d. Drug safety and efficacy were assessed before each dosage reduction. During the study period, 130 adult patients underwent 137 OLTs. Thirty patients fulfilled the entry criteria and were administered prophylaxis with amphotericin B lipid complex. No patient developed proven IFI during prophylaxis. Cultures from normally sterile sites (blood and abdominal drain fluid) always showed negative results. All fungal isolates were sensitive in vitro to amphotericin B. There was no significant difference in colonization scores among the groups of patients administered different dosages of amphotericin B lipid complex. No death, serious adverse reaction, or nephrotoxicity was attributed to amphotericin B lipid complex. We conclude that prophylaxis with amphotericin B lipid complex targeted to patients requiring prolonged ICU treatment after OLT appears to be well tolerated and may prevent IFI. Our current policy is to use amphotericin B lipid complex, 1 mg/kg/d, as antifungal prophylaxis in this high-risk group.

Adult↗
PubMed2000

p53 binds selectively to the 5' untranslated region of cdk4, an RNA element necessary and sufficient for transforming growth factor beta- and p53-mediated translational inhibition of cdk4.

One consequence of transforming growth factor beta (TGF-beta) treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show that the 5' untranslated region (UTR) of the cdk4 mRNA is both necessary and sufficient for wild-type p53-dependent TGF-beta-regulated translational inhibition of cdk4. Wild-type p53 bound selectively to the 5' UTR of the cdk4 mRNA and inhibited translation of RNAs that contain this region. RNA binding and translational control are two genetically separable functions of p53, as are specific and nonspecific RNA binding. Moreover, transactivation-defective mutants of p53 retain the ability to regulate cdk4 translation. Our findings suggest that p53 functions as a regulator of translation in response to TGF-beta in vivo.

5' Untranslated Regions↗
PubMed2000

Triple central ray amputation for clear cell sarcoma of the hand.

A 16-year-old girl presented for evaluation and management of a recurrent soft-tissue mass in her left hand after excision at another facility. She was given a diagnosis of clear cell sarcoma. She chose a limb salvage procedure over amputation. A triple central ray amputation of her index, middle, and ring fingers was performed. After 3 years, she has reasonable grasp function with her remaining fingers and has chosen not to use a prosthesis. Long-term follow-up is necessary for this tumor, as local recurrence and metastatic disease have been reported frequently.

Adolescent↗
PubMed1999

Amine-catalyzed addition of azide ion to alpha,beta-unsaturated carbonyl compounds.

[formula: see text] A new protocol for the beta-azidation of alpha,beta-unsaturated carbonyl compounds is described. The method employs tertiary amines as catalysts for azide addition. The azide source is a 1:1 mixture of TMSN3 and AcOH. Tertiary amines, either in solution or bound to a solid support, are efficient catalysts for the reaction.

Amines↗
PubMed1999

Adjunctive treatment of enchondromas with CO2 laser.

STUDY DESIGN/MATERIALS AND METHODS: Fourteen enchondromas, in eight patients, involving the tubular bones of the hand, were treated with curettage, CO2 laser sterilization of the tumor margins followed by autologous bone grafting. Average follow-up time was 35.4 months (14-106 months). Average patients age was 29 years. RESULTS: At follow-up there were no clinical recurrences, none had pain, and all patients reported satisfactory hand function without limitations. Minimal decrease in range of motion without functional limitation was encountered following excision of two lesions (14%) in one patient. One patient reported an increase in range of motion after excision. Grip strength was only minimally decreased. There was no radiographic evidence of recurrence. CONCLUSION: The use of CO2 laser is safe and effective as an adjunct to curettage and bone grafting in the management of relatively large enchondromas of the tubular bones of the hand.

Adolescent↗
PubMed1999

Spontaneous multivessel coronary artery dissection: repeated presentation in a healthy postmenopausal woman.

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction which is infrequently diagnosed antemortem. Most previously reported cases were found in women of whom a significant proportion presented during pregnancy or the postpartum period. We describe the first antemortem case of spontaneous coronary artery dissection, unrelated to pregnancy or the postpartum state, which ultimately resulted in diffuse involvement of both the left and right coronary arteries over a period of 4 months. Pathophysiology and case management of this disorder are discussed.

Adult↗
PubMed1999

The development of a structured rating schedule (the BAS) to assess skills in breaking bad news.

There has been considerable interest in how doctors break bad news, with calls from within the profession and from patients for doctors to improve their communication skills. In order to aid clinical training and assessment of the skills used in breaking bad news there is a need for a reliable, practical and valid, structured rating schedule. Such a rating schedule was compiled from agreed criteria in the literature. Video-taped recordings of simulated consultations breaking bad news were independently assessed by three raters using the schedule and compared to three experts who gave global ratings. The primary outcome measures were internal consistency of the schedule and level of agreement between raters. The internal consistency was high with a Cronbach's alpha of 0.93. Agreement between raters using the schedule was moderate to good. The majority of the variation in scores was due to the differences in skills demonstrated in the interviews. The agreement between raters not using the schedule was poor. The BAS provides a simple to use, reliable, and consistent rating schedule for assessing skills used in breaking bad news. It could be a valuable aid to teaching this difficult task.

Adult↗
PubMed1999

A phase II study of [90Y] yttrium-capromab pendetide in the treatment of men with prostate cancer recurrence following radical prostatectomy.

There is currently no curative therapy for men who have disseminated prostate cancer following failed radical prostatectomy. The purpose of this trial was to investigate systemic radioimmunotherapy in these men. Eight patients with occult metastatic prostate cancer following radical prostatectomy as evidenced solely by a rising serum PSA and evidence of soft tissue lesions outside the prostatic fossa detected by an [111I]indiumcapromab pendetide scan received an infusion of 10 mg of capromab pendetide labeled with 9 mCi/m2 of [90Y]yttrium. Serum PSA was used to measure response rate. There were no complete or partial responses by PSA criteria. Significant unexpected bone marrow toxicity developed in the first 6 of 8 patients treated. The last two patients received co-infusion of edetate calcium disodium in an effort to decrease marrow suppression. In these two patients less marrow toxicity was seen. Repeat 111In-capromab pendetide scans were uninterpretable due to grossly altered whole-body biodistribution of the radioimmunoconjugate. Retrospective analysis of serial PSA values after closure of the study showed a decrease in the log slope PSA for seven of eight patients following radioimmunotherapy, with a statistically significant change in the mean log slope (p = 0.01). The clinical significance of this small but measurable change is uncertain. We conclude that radioimmunotherapy for occult metastatic prostate cancer using 90Y-capromab-pendetide at the dose described does not lower serum PSA, is associated with significant hematologic toxicity, and leads to complexation of the immunoconjugate following subsequent capromab pendetide infusion.

Adenocarcinoma↗