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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 73 records · Page 4Linked to original sources
PubMed2000

Eye-wall resection.

PURPOSE: To review the ocular retention rates, visual results, and metastases in uveal tumors managed with eye-wall resection techniques. METHODS: This was a retrospective analysis of uveal tumors selected for eye-wall resection with the surgical procedures performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data was performed. RESULTS: A total of 132 eyes were scheduled for eye-wall resection surgery. Mean patient age was 52 years (range, 11 to 86 years). Tumors involved the iris alone in 17 cases, the iris-ciliary body in 53, the ciliary body alone in 16, and the choroid (ciliochoroidal, iris-ciliary body-choroid, or choroid) in 46 cases. A total of 114 eyes harbored melanomas; tumors located more posteriorly were more likely to have epithelioid cells (P < .05). Mean follow-up was 6 years. Mean number of clock hours in iris and iris-ciliary body tumors was 3.5. In tumors that involved the choroid, the mean largest diameter was 12.6 mm and the mean thickness was 8.2 mm. Ninety-three (70%) of 132 eyes were retained. Histologic assessment of surgical margins did not correlate with either evidence of tumor in enucleated eyes or metastatic disease. Surgical margins of tumors located more anteriorly were more likely to be clear on histologic evaluation (P < .05). Approximately 56% of retained eyes had a final visual acuity of 20/40 or better; visual results were significantly better in tumors located more anteriorly (P < .05). All retained eyes with iris tumors had a final visual acuity of 20/40 or better. In tumors that involved the choroid, 8 of 25 retained eyes kept visual acuity of 20/40 or better. Metastases developed in 8 patients; all metastatic events developed in patients with tumors that involved the choroid, and 7 of 8 were mixed cell melanomas. CONCLUSIONS: Seventy percent of eyes were retained, and 56% of these had a final visual acuity of 20/40 or better. Only 7% of patients with uveal melanoma developed metastatic disease (mean follow-up, 6 years). Survival did not appear to be compromised with eye-wall resection, and in very thick melanomas located more posteriorly, ocular retention and visual results appeared to be better than that attained with radiation alone.

Adolescent↗
PubMed1999

Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II.

The product of the human oncogene ELL encodes an RNA polymerase II transcription factor that undergoes frequent translocation in acute myeloid leukemia (AML). In addition to its elongation activity, ELL contains a novel type of RNA polymerase II interaction domain that is capable of repressing polymerase activity in promoter-specific transcription. Remarkably, the ELL translocation that is found in patients with AML results in the deletion of exactly this functional domain. Here we report that the EAP30 subunit of the ELL complex has sequence homology to the Saccharomyces cerevisiae SNF8, whose genetic analysis suggests its involvement in the derepression of gene expression. Remarkably, EAP30 can interact with ELL and derepress ELL's inhibitory activity in vitro. This finding may reveal a key role for EAP30 in the pathogenesis of human leukemia.

Amino Acid Sequence↗
PubMed1999

Quantum-well states as fabry-Perot modes in a thin-film electron interferometer

Angle-resolved photoemission from atomically uniform silver films on iron (100) shows quantum-well states for absolutely determined film thicknesses ranging from 1 to approximately 100 monolayers. These states can be understood in terms of Fabry-Perot modes in an electron interferometer. A quantitative line shape analysis over the entire two orders of magnitude of thickness range yields an accurate measurement of the band structure, quasiparticle lifetime, electron reflectivity, and phase shift. Effects of confinement energy gap, reflection loss, and surface scattering caused by controlled roughness are demonstrated.

Journal Article↗
PubMed1999

A diazo-2 study of relaxation mechanisms in frog and barnacle muscle fibres: effects of pH, MgADP, and inorganic phosphate.

The aim of this study was to compare the effects of increased concentrations of MgADP, inorganic phosphate (Pi) and H+ ([MgADP], [Pi] and [H+], respectively) on the rate of relaxation in two different muscle types: skinned muscle fibres from the frog Rana temporaria and myofibrillar bundles from the giant Pacific acorn barnacle Balanus nubilus. Relaxation transients are produced by the photolysis of diazo-2 and are well fitted with a double exponential curve, giving two rate constants: k1 [5.6+/-0.1 s-1 for barnacle, n=30; 26.3+/-0.7 s-1 for frog, n=14 (mean+/-SEM)] and k2 [0.6+/-0.1 s-1 in barnacle, n=30; 10.4+/-1.0 s-1 in frog, n=14 (mean+/-SEM)], at 10 degrees C. Decreasing the pH by 0.5 pH units did not significantly affect k1 for barnacle relaxation [5.6+/-0.1 s-1 (mean+/-SEM), n=15] compared to the decrease in k1 of 40% seen in frog. Use of the Ca2+-sensitive fluorescent label acrylodan on barnacle wild-type troponin C demonstrated that decreasing the pH from 7.0 to 6.6 only alters the pCa50 value by 0.23 in the cuvette, while stopped-flow experiments with acrylodan revealed no significant change in koff from the labelled protein [322+/-32 s-1 at pH 7.0 and 381+/-24 s-1 (mean+/-SEM) at pH 6.6]. Increasing [MgADP] by 20 microM (50 microM added ADP) from control values of 50 microM in frog decreased k1 to 12.3+/-0.4 s-1 (mean+/-SEM, n=8), and at 400 microM MgADP, k1=9.6+/-0.1 s-1 (mean+/-SEM, n=12). In barnacle, 500 microM MgADP had a much smaller effect on k1 (4.0+/-0. 9 s-1, mean+/-SEM, n=8). Increasing the free [Pi] from the contaminant level of 0.36 mM to 1.9 mM slowed k1 by approximately 15% in barnacle [4.8+/-0.8 s-1, mean+/-SEM, n=7], compared to a approximately 30% reduction seen in frog. We conclude that the differences between barnacle and frog seen here are most probably due to different isomers of the contractile proteins, and that events underlying the crossbridge cycle are the same or similar. We interpret our results according to a model of crossbridge transitions during relaxation.

2-Naphthylamine↗
PubMed1999

Characterisation of a mutant of barnacle troponin C lacking Ca2+-binding sites at positions II and IV.

This study investigates a mutant barnacle troponin C (TnC) protein (BTnC2-4-) in which the Ca2+-binding sites (sites II and IV) have been rendered non-functional. Eliminating Ca2+ binding at both Ca2+-binding sites of barnacle TnC did not prevent the incorporation of BTnC2-4- into TnC-depleted myofibrillar bundles, although, as expected, the mutant was not able to effect muscle regulation. We conclude that the Mg2+ involved in stabilising the interaction between TnC and TnI in the barnacle must bind at a separate location to the Ca2+-binding sites. Competition experiments between BTnC2-4- and wild-type barnacle TnC (BTnCWT) or the native isoform BTnC2 indicate that BTnC2-4- has an approximately fourfold higher affinity for barnacle TnI than BTnCWT but a lower affinity for TnI compared to BTnC2. These results indicate that disabling sites II and IV changes the affinity of BTnC2-4- for TnC-denuded barnacle myofibrils, altering the stability of the bond formed between TnC and the thin filament.

Animals↗
PubMed1999

Investigation of a genetically engineered mutant of barnacle troponin C containing a central helix deletion.

To examine the importance of the central alpha-helix of troponin C (TnC) we have bacterially expressed one of the isoforms of barnacle TnC (BTnC2), BTnCWT, but without the aspartate residue at position 80 in the central helix (BTnC80-). This manipulation is expected to produce an approximately 100 degrees axial rotation of the C-domain with respect to the N-domain, and a net charge change of -1. BTnC80- mutant was able to restore force to TnC-depleted skinned barnacle myofibrillar bundles to a greater extent than wild-type protein (approximately = 170%). Competition experiments between BTnC80- and BTnC2-4-, a mutant lacking both of the calcium-specific sites (sites II and IV), shows that deletion of a single amino acid in the central helix results in a protein with increased affinity for the thin filament and one that is bound preferentially compared to BTnC2-4- when at equimolar concentrations.

Animals↗
PubMed1999

An introductory hospice experience for third-year medical students.

BACKGROUND: An organized and distinct curriculum in hospice and palliative care education is lacking in most United States medical school programs. Because of this knowledge deficit, physicians are often not able to meet the needs of their terminally ill patients and their families. METHODS: A five-day combined didactic and clinical rotation in hospice and palliative care for third-year medical students was developed and is presented. The program is run through a home-based hospice in conjunction with the state's medical school. RESULTS: The pilot program has been well accepted by the participating students as a valuable learning experience. Although brief, it has also been successful in changing some of their attitudes about death and the care of the dying. CONCLUSIONS: This one-week program is an effective means to provide an intense course in hospice education. It should be easily transportable to other health care curricula.

Attitude to Death↗
PubMed1999

Low-dose oral administration of interferon-alpha for the treatment of immune-mediated keratoconjunctivitis sicca in dogs.

This preliminary study was designed to evaluate the effectiveness and dosage of oral use of interferon-alpha (IFN-alpha) in the treatment of naturally occurring, immune-mediated, canine keratoconjunctivitis sicca (KCS). Dogs with chronic immune-mediated KCS were selected from the two clinic populations. All medication, except topical artificial tears, was discontinued at least 2 weeks prior to beginning the clinical trial. IFN-alpha was administered orally once daily to the dogs by their owners as the sole therapy for the KCS. Examinations of the dogs were performed every 2 weeks for the duration of the trial (12 weeks). Each dog was given either two or three separate, escalating doses (20, 40, 80 IU of the IFN-alpha. A favorable response was observed in 55% (11/20) of all dogs treated. Clinical findings of those dogs that responded included increased wetting of the eyes, decreased mucus discharge, and fewer signs of discomfort. There was a nearly significant difference (p = 0.08) in pretreatment mean Schirmer's tear test (STT) between the dogs that responded (6.4 +/- SEM 0.62 mm/min) and those that did not respond (4.7 +/- SEM 0.69 mm/min) to the orally administered IFN-alpha. Seven of 11 dogs with favorable outcomes had an increased STT of at least 5 mm/min after treatment with oral IFN-alpha and the group had a post-treatment STT (10.5 +/- SEM 1.4 mm/min) significantly greater than baseline (p = 0.0004). The post-treatment STT of the dogs that did respond was significantly greater (p < 0.01) than the post-treatment mean STT of dogs that did not respond. All dogs that responded did so with the 20 or 40 IU dose of IFN-alpha. No side effects were noted and all dogs tolerated the treatment well.

Administration, Oral↗
PubMed1999

Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases.

AIM: To evaluate the clinical features, treatment results, and recurrence rates in patients with either intraepithelial or invasive squamous cell carcinoma of the conjunctiva. METHODS: Retrospective analysis of 60 cases (22 conjunctival intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns of clinical presentation, aetiological factors, and treatment results. The mean patient age was 64 years old. 70% of the patients were male. Patients were treated with a variety of therapies, depending on the degree of tumour involvement; most cases were treated with frozen section controlled excision and adjunctive cryotherapy. Modified eye wall resection or enucleation was done for intraocular invasion and exenteration was done for orbital involvement. RESULTS: Red eye (68%) and ocular irritation (57%) were the most common presenting symptoms. 44% of the patients had other eye findings consistent with extensive solar exposure. 20% of the patients had a history of malignant skin tumours. Visceral malignancies developed in 8%. Scleral involvement was present in 14 (37%), intraocular involvement in five (13%), and orbital invasion in four (11%) cases with invasive squamous cell carcinoma. After a mean follow up of 56 months (18-226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient developed metastases or tumour related deaths. CONCLUSION: Excision with intraoperative control of the surgical margins and adjunctive cryotherapy results in good tumour control rates.

Adult↗
PubMed1999

A critical analysis of the pharmacology of AZT and its use in AIDS.

The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells. Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters. A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT. HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent. Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination). However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action. Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect. However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients. Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.

Anti-HIV Agents↗
PubMed1999

Homologous chromosome pairing in wheat.

Bread wheat is a hexaploid (AABBDD, 2n=6x=42) containing three related ancestral genomes, each having 7 chromosomes, giving 42 chromosomes in diploid cells. During meiosis true homologues are correctly associated in wild-type wheat, but a degree of association of related chromosomes (homoeologues) occurs in a mutant (ph1b). We show that the centromeres are associated in non-homologous pairs in all floral tissues studied, both in wild-type wheat and the ph1b mutant. The non-homologous centromere associations then become homologous premeiotically in wild-type wheat in both meiocytes and the tapetal cells, but not in the mutant. In wild-type wheat, the homologues are colocalised along their length at this stage, but the telomeres remain distinct. A single telomere cluster (bouquet) is formed in the meiocytes only by the onset of leptotene. The sub-telomeric regions of the homologues associate as the telomere cluster forms. The homologous associations at the telomeres and centromeres are maintained through meiotic prophase, although, during leptotene, the two homologues and also the sister chromatids within each homologue are separate along the rest of their length. As meiosis progresses, first the sister chromatids and then the homologues associate intimately. In wild-type wheat, first the centromere grouping, then the bouquet disperse by the end of zygotene.

Meiosis↗
PubMed1999

Use of a custom retrograde intramedullary rod for the management of distal femoral nonunion: a report of two cases.

Nonunion of the distal femur is a rare injury that is difficult to manage. A variety of surgical implants and techniques are available. We present an alternative mode of treatment for supracondylar femoral nonunion using a custom retrograde titanium femoral nail (Biomet; Warsaw, IN) to successfully achieve union in two cases. We believe the added length, custom modifications, and enhanced stability allowed better fixation in an osteopenic distal femur.

Adult↗
PubMed1999

An evaluation of WHA resolution 45.5: health human resource implications.

The World Health Assembly approved resolution WHA45.5 in 1992. This paper reports the findings of an evaluation of the implementation of this resolution using a survey technique. A total of 150 WHO Member States responded, for a 79% response rate. Findings suggest that the greatest strides worldwide have been made in education. While the data show that progress has been made at the country level, far more action is needed to strengthen nursing and midwifery if these cost-effective resources are to play a decisive role in improving the extent and quality of services, especially as delivered to people in the greatest need.

Cross-Sectional Studies↗
PubMed1998

Catheter complications in AIDS patients treated for cytomegalovirus retinitis.

PURPOSE: To describe the complications of central venous catheter use for intravenous therapy of cytomegalovirus (CMV) retinitis in patients with AIDS. METHODS: Retrospective review of 388 patients with AIDS and CMV retinitis treated with intravenous medications through an indwelling catheter. RESULTS: The catheter complication rate was 1.2 complications per person-year (0.33 complications per 100 catheter-days). Current injecting drug use increased the risk of infectious complications [hazard ratio (HR), 1.73; P=0.04] whereas former use did not (HR, 0.96; P=0.88). Subdermal port catheters increased the risk of bacteremia (HR, 1.78; P=0.05). Mortality for the first complication was 5.8%. Forty percent of patients required catheter removal, and 86.8% of these patients required reinsertion of another catheter. CONCLUSIONS: Catheter complications are a substantial problem in patients with CMV retinitis treated with daily intravenous therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Cervical epidural steroid injection with intrinsic spinal cord damage. Two case reports.

STUDY DESIGN: Intrinsic cervical spinal cord damage represents the serious and permanent complications that can occur if cervical epidural steroid injections are administered while the patient is sedated. Two case reports are presented. OBJECTIVES: To draw attention to the dangerous consequences that can arise from sedating a patient before administering a cervical epidural steroid injection. SUMMARY OF BACKGROUND DATA: Reported complications of cervical epidural steroid injections have been minor and infrequent. No reports of intrinsic cervical cord damage could be found in a comprehensive English language literature search. METHODS: Two case reports of permanent intrinsic cervical cord damage in patients who had been administered cervical epidural steroid injections while under intravenous sedation are presented. Magnetic resonance imaging was performed before and after the administration of cervical epidural steroid injections. Each patient had herniated nucleus pulposus before they received cervical epidural steroid injections and intrinsic cord damage on postinjection magnetic resonance images. RESULTS: Both patients developed increased pain and neurologic symptoms within 24 hours of injection. To date, these symptoms appear to be permanent. However, Patient 1 had pain relief in her right arm and shoulder after undergoing a microdiscectomy, but pain was still persistent in her left leg, and she has developed a positive Lhermitte's sign. CONCLUSION: These case reports indicate fluoroscopic guidance will not insure or prevent intrathecal perforation or spinal cord penetration during the administration of cervical epidural steroid injections. In addition, although intravenous sedations during cervical epidural steroid injections have been used numerous times without reported complications, it appears intravenous sedation in these two cases resulted in the inability of the patient to experience the expected pain and paresthesias at the time of spinal cord irritation. Therefore, the authors conclude that the patient should be fully awake during the administration of cervical epidural steroid injections, with only local anesthetic in the skin used for analgesia.

Adult↗
PubMed1998

Irrigation in facial and scalp lacerations: does it alter outcome?

STUDY OBJECTIVE: Animal and human studies suggest that irrigation lowers the infection rate in contaminated wounds, but there is no evidence that this common practice is beneficial for "clean" lacerations. We tested the null hypothesis that there is no difference in the infection rate for noncontaminated lacerations to the face and scalp that are irrigated before primary closure compared with similar wounds that are closed primarily without irrigation. METHODS: We performed a cross-sectional study of consecutive patients presenting to a suburban, academic emergency department between October 1992 and August 1996. Patients with nonbite, noncontaminated facial skin or scalp lacerations who presented less than 6 hours after injury were included. Structured, closed-question data collection instruments were completed at the time of laceration repair and at suture removal. The primary outcome parameters were the incidence of wound infection and the short-term cosmetic appearance of lacerations in patients who did or did not receive irrigation. RESULTS: A total of 1,923 patients were included in the study group; 1,090 patients received saline irrigation, and 833 patients did not. The irrigation and nonirrigation groups were similar with regard to time from injury to presentation (1.56 versus 1.42 hours, respectively), frequency of linear wound morphology (82% versus 88%), frequency of smooth wound margins (72% versus 82%), number of layers of closure (1.14 versus 1.26), number of skin sutures applied (4.98 versus 4.65), number of deep sutures applied (.70 versus 1.05), and use of oral antibiotic prophylaxis (2.8% versus 4.0%). With respect to outcomes, the incidence of wound infection was not significantly different between the two treatment groups (.9% versus 1.4%, respectively; P = .28). Likewise, the percentage of patients who had an "optimal" cosmetic appearance was similar in the two groups (75.9% versus 81.7%, respectively; P = .07). CONCLUSION: Irrigation before primary closure did not significantly alter the rate of infection or the cosmetic appearance in our study population with clean, noncontaminated facial and scalp lacerations.

Adolescent↗