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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 145 records · Page 8Linked to original sources
PubMed2000

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Aged↗
PubMed2000

A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia.

Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either 2.5 or 5 microg/kg/day of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or a placebo administered subcutaneously after completion of chemotherapy. The study evaluated the toxicity of PEG-rHuMGDF and any effect on the duration of thrombocytopenia. Each of 35 patients under 60 years of age received the following therapy: 45 mg/m(2) daunorubicin on days 1-3, 100 mg/m(2) cytarabine (ARA-C) for 7 days, and 2 gm/m(2) high-dose ARA-C (HIDAC) for 6 doses on days 8-10. The 22 patients 60 years or older received standard daunorubicin and ARA-C without HIDAC. PEG-rHuMGDF was well tolerated, and no specific toxicities could be attributed to its use. There was no difference in the time to achieve a platelet count of at least 20 x 10(9)/L among the 3 groups (median 28-30 days for patients less than 60 years old and 21-23 days for patients 60 years or older). Patients receiving PEG-rHuMGDF achieved higher platelet counts after remission. However there was no significant difference in the number of days on which platelet transfusions were administered among the 3 groups. The complete remission rate was 71% for patients less than 60 years and 64% for those 60 years or older, with no significant difference among the 3 groups. Postremission consolidation chemotherapy with either placebo or PEG-rHuMGDF was given to 28 patients beginning the day after completion of chemotherapy. There was no apparent difference in the time that was necessary to reach a platelet count of at least 20 or 50 x 10(9)/L or more platelets or in the number of platelet transfusions received. In summary, PEG-rHuMGDF was well tolerated by patients receiving induction and consolidation therapy for AML; however, there was no effect on the duration of severe thrombocytopenia or the platelet transfusion requirement. (Blood. 2000;95:2530-2535)

Acute Disease↗
PubMed2000

Telomerase activity and expression of telomerase subunits in the testicular tissue of infertile patients.

OBJECTIVE: Determination of telomerase activity and the expression of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in the testicular tissue of patients with infertility arising from various causes. DESIGN: Prospective observational study. SETTING: A university hospital. PATIENT(S): Thirty-three patients with azoospermia arising from various causes. There were 12 testicular biopsy specimens from patients with Sertoli cell-only syndrome, 9 from patients with maturation arrest, and 12 from patients with obstructive azoospermia and normal histologic findings. INTERVENTION(S): Thirty-three testicular biopsies. MAIN OUTCOME MEASURE(S): Correlation of histologic findings at testicular biopsy with telomerase activity, hTERT, and hTR. RESULT(S): All 12 biopsy specimens from patients with obstructive azoospermia were positive for telomerase activity, hTR, and hTERT. Biopsy specimens from the 9 patients with maturation arrest were positive for telomerase activity in 8 cases, hTR in 9 cases, and hTERT in 5 cases. None of the patients with Sertoli cell-only syndrome showed either telomerase activity or hTERT, but all of them showed hTR. CONCLUSION(S): Telomerase activity and evidence of hTERT in testicular tissue are highly sensitive and highly specific markers of gametogenesis, which could gain in importance as part of the fertility workup before microinjection procedures.

DNA-Binding Proteins↗
PubMed2000

Mechanical properties of brain tissue in-vivo: experiment and computer simulation.

Realistic computer simulation of neurosurgical procedures requires incorporation of the mechanical properties of brain tissue in the mathematical model. Possible applications of computer simulation of neurosurgery include non-rigid registration, virtual reality training and operation planning systems and robotic devices to perform minimally invasive brain surgery. A number of constitutive models of brain tissue, both single-phase and bi-phasic, have been proposed in recent years. The major deficiency of most of them, however, is the fact that they were identified using experimental data obtained in vitro and there is no certainty whether they can be applied in the realistic in vivo setting. In this paper we attempt to show that previously proposed by us hyper-viscoelastic constitutive model of brain tissue can be applied to simulating surgical procedures. An in vivo indentation experiment is described. The force-displacement curve for the loading speed typical for surgical procedures is concave upward containing no linear portion from which a meaningful elastic modulus might be determined. In order to properly analyse experimental data, a three-dimensional, non-linear finite element model of the brain was developed. Magnetic resonance imaging techniques were used to obtain geometric information needed for the model. The shape of the force-displacement curve obtained using the numerical solution was very similar to the experimental one. The predicted forces were about 31% lower than those recorded during the experiment. Having in mind that the coefficients in the model had been identified based on experimental data obtained in vitro, and large variability of mechanical properties of biological tissues, such agreement can be considered as very good. By appropriately increasing material parameters describing instantaneous stiffness of the tissue one is able, without changing the structure of the model, to reproduce experimental curve almost perfectly. Numerical studies showed also that the linear, viscoelastic model of brain tissue is not appropriate for the modelling brain tissue deformation even for moderate strains.

Animals↗
PubMed2000

Constitutive modelling of abdominal organs.

Abdominal organs are very susceptible to trauma. In order to protect them properly against car crash and other impact consequences, we need to be able to simulate the abdominal organ deformation. Such simulation should account for proper stress-strain relation as well as stress dependence on strain rate. As the step in this direction, this paper presents three-dimensional, non-linear, viscoelastic constitutive models for liver and kidney tissue. The models have been constructed basing on in vivo experiments conducted in Highway Safety Research Institute and the Medical Centre of The University of Michigan (Melvin et al., 1973). The proposed models are valid for compressive nominal strains up to 35% and fast (impact) strain rates between 0.2 and 22.5 s(-1). Similar models can find applications in computer and robot assisted surgery, e.g. the realistic simulation of surgical procedures (including virtual reality) and non-rigid registration.

Abdominal Injuries↗
PubMed2000

Sodium detection during the water absorption response in Rana pipiens.

Although taste in vertebrates is typically associated with specialized receptors in the lingual epithelium, Hoff and Hillyard reported that the toad, Bufo punctatus, is able to "taste" sodium with the abdominal skin. This was reflected in a differential behavioral response to hypertonic NaCl. The present study tests for the presence of such abdominal chemoreceptors in the frog Rana pipiens. The experiment was a five-condition design in which frogs were placed on filter paper saturated with: deionized water, 250 mM NaCl, 350 mM NaCl, 12.9 microM amiloride, or 350 mM NaCl + 12.9 microM amiloride. The time that the frogs remained on the test substrate before moving to a surface of deionized water was recorded. It was necessary to dehydrate the frogs to 80% of their body weight to elicit a behavioral response to the NaCl whereas dehydration to 90% of their body weight has been reported effective in Bufo punctatus. The frogs displayed significantly shorter mean times to move on both concentrations of NaCl compared to deionized water, with the shortest times occurring when 350 mM NaCl was used. Amiloride alone did not have an effect upon times to move to deionized water, but did significantly reduce the response to 350 mM NaCl. Movement to amiloride + 350 mM NaCl did not differ significantly from that to deionized water. The results indicate that Rana pipiens, like Bufo punctatus, have epithelial chemoreceptors for the detection of NaCl on hydrated surfaces and that these receptors, like those of mammals, are amiloride sensitive.

Abdomen↗
PubMed2000

Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia.

OBJECTIVES: To investigate the urodynamic effects and tolerability of the new antimuscarinic drug tolterodine in children with detrusor hyperreflexia. METHODS: Twenty-two children (12 boys and 10 girls; age range 3 months to 15 years, mean age 5.7 years) with detrusor hyperreflexia resulting in maximum detrusor pressures exceeding 40 cm H(2)O during filling cystotonometry were enrolled to receive tolterodine tartrate (a total of 0.1 mg/kg orally daily, divided into two doses) either as a first-line therapy (n = 12, group 1) or replacing oxybutynin chloride therapy (n = 10, group 2). Within 3 months, all patients underwent urodynamic re-evaluation during ongoing tolterodine treatment. RESULTS: In group 1, the mean maximum bladder capacity increased from 120.2 to 173.0 mL (+44%), the mean detrusor compliance increased from 8.7 to 13.5 mL/cm H(2)O (+55%), and the mean maximum detrusor pressures decreased from 70.1 to 37.9 cm H(2)O (-46%); the differences were significant (P < 0.001). In group 2, no differences in the urodynamic effects of oxybutynin versus tolterodine were noted. Only 1 patient experienced a transient and moderately adverse effect with tolterodine. CONCLUSIONS: Although based on a limited number of subjects, these data indicate that in pediatric patients with detrusor hyperreflexia, tolterodine may be better tolerated than and equally effective as the standard drug oxybutynin chloride.

Adolescent↗
PubMed2000

Alloreactivity of umbilical cord blood mononuclear cells: specific hyporesponse to noninherited maternal antigens.

Earlier studies noted that patients who underwent cord blood (CB) transplantation had a lower incidence of graft-versus-host disease (GVHD) than those who underwent bone marrow transplantation (BMT). The premise that the immune reactivity of CB mononuclear cells (CB-MNC) to HLA mismatched combinations and to noninherited maternal antigens (NIMA) may be one of the factors involved in this phenomenon is still debatable. In this study we have attempted to evaluate the alloresponse and alloreactivity induced by CB-MNC by means of the standard mixed lymphocyte reaction test (SMLR) and the more sensitive, modified mixed lymphocyte reaction test (MMLR). Both techniques were used to test CB-MNC (n = 28) against HLA class II mismatched MNC from mothers (n = 26), fathers (n = 12), and unrelated individuals (n = 60) who served as controls. Alloresponse capabilities and stimulation capacities of CB-MNC in the SMLR were similar to those of control MNC: relative response (RR) = 73 vs. 65 and 58 vs. 65, respectively. Similar results were obtained in the MMLR. CB-MNC responded weakly to the maternal MNC in comparison with control MNC (RR = 47 vs. 73 [p = 0.0099]), while a stronger response was noted to the paternal than the maternal MNC (RR = 72 vs. 47 [p = 0.045]). Our results demonstrate that CB-MNC both respond to and induce alloresponse in HLA mismatched combinations. Moreover, the hyporesponse of CB-MNC to maternal cells that we observed suggests a form of tolerance to NIMA, which is probably due to the fetus's exposure to these antigens in its intrauterine life.

Female↗
PubMed2000

Chronic sequels after thoracoscopic procedures for benign diseases.

OBJECTIVE: Chronic pains after lateral thoracotomy are present in up to 40% of cases. Chronic sequels after thoracoscopy are less common, but nevertheless, a cause for complaints by patients. Pain often reflects a recurrence of malign disease. For this reason, we only investigated patients with benign disease. METHODS: We retrospectively investigated the incidence of chronic sequels in a consecutive series of 161 patients who underwent thoracoscopy for benign disease and were not converted to an open procedure. The data from all 144 patients, contactable at the time of investigation, who were at least 2 months postsurgery, were analyzed. RESULTS: Chronic sequels were present in an overall of 31.4% of patients. Patients complained of chronic pain (20.1%), numbness distal to the incision sites (16.9%) and disaesthesia (8.3%). Painkillers are taken on a regular basis by 82.8% of patients with chronic pain. The use of Staplers, as well as the number of drains (1 vs. 2) used, were statistically significant (P>0.05) for chronic sequels. All other investigated factors, such as sex, age, and length of drainage, were not significantly different in the two groups. CONCLUSION: The thoracoscopic approach is not likely to impact on the prevalence of long-term postthoracotomy sequels, and therefore, further strengths are necessary to reduce this number.

Adolescent↗
PubMed2000

Measurement of endotracheal tube cuff leak to predict postextubation stridor and need for reintubation.

BACKGROUND: The purpose of this study was to determine the predictive value of an endotracheal tube cuff leak for the development of postextubation stridor and the need for reintubation. STUDY DESIGN: Consecutive trauma patients who required intubation at a level I trauma center from July 1997 to July 1998 were studied prospectively. Pediatric patients and those who did not meet the standard weaning protocol criteria established by the Division of Trauma and Surgical Critical Care were excluded. Injury Severity Score, endotracheal tube size, reason for intubation, and the number of days intubated before the initial extubation attempt were recorded. At the time of extubation, the difference in exhaled tidal volume from before to after endotracheal tube cuff deflation was calculated. This number was then divided by the exhaled tidal volume before cuff deflation and was recorded as the percent cuff leak. Patients were followed for 24 hours after extubation for the development of stridor or need for reintubation. Statistical analysis to compare subgroups of patients was performed using ANOVA with Scheffé post hoc analysis. RESULTS: Among the 110 patients analyzed, the most common reason for intubation was closed-head injury. Seven patients (6.4%) developed stridor alone and had a mean cuff leak of 5 8 mL (8.4% of tidal volume before cuff deflation). Six patients (5.5%) experienced stridor that required reintubation and had a mean cuff leak of 68 mL (9.2% of tidal volume before cuff deflation). Patients who developed stridor or needed reintubation had been intubated for a significantly greater length of time than those not developing stridor or requiring reintubation (2.6 versus 3.0 days, p < 0.001). There were no differences in Injury Severity Score, endotracheal tube size, or reason for intubation between these groups. CONCLUSIONS: A cuff leak of less than 10% of tidal volume before cuff deflation is useful in identifying patients at risk for stridor or reintubation (96% specificity). It appears that the amount of cuff leak decreases after intubation for more than 3 days, increasing the risk of stridor and need for reintubation. This information may be helpful in identifying those patients who need treatment for laryngotracheal edema, ie, use of steroids or anesthesia during extubation, the efficacy of which remains to be determined.

Craniocerebral Trauma↗
PubMed2000

Infiltrating T cells during liver graft-versus-host disease show a restricted T-cell repertoire.

Data from animal models have shown that hepatic graft-versus-host disease (GVHD) may be mediated by donor T cells interacting with liver adhesion molecules, other minor histocompatibility antigens, or both. We hypothesized that T-cell infiltrates within a liver biopsy during clinical GVHD would show a restricted T-cell response because the T cells would be responding to a limited number of antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD after a matched sibling bone marrow transplantation for acute myeloid leukemia. Spectratype analysis of peripheral blood at the time of liver GVHD revealed that the patient had reconstituted a complex peripheral T-cell repertoire as evidenced by the presence of complementarity-determining region 3 (CDR3) length heterogeneity in most of the T-cell families. The repertoire complexity was skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype analysis on the liver biopsy sample revealed a limited infiltrate with an oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in more detail by sequencing the relevant expansions noted by spectratype and developing probes for the predominant CDR3 sequences. These clonotype probes were hybridized to peripheral blood and liver samples from the patient, a T-cell line developed from the patient's peripheral blood at the time of the initial skin GVHD, the donor's blood and marrow, and control samples. The results showed that the T-cell infiltrate during liver GVHD is mediated by a limited number of T cells, and that those cells are mostly different from the ones expanded from the peripheral blood during an acute skin GVHD reaction. These data support the concept that liver GVHD is a response to tissue-specific minor histocompatibility antigens.

Acute Disease↗
PubMed2000

Concomitment spread of a renal cell carcinoma beyond the kidney and a transitional cell carcinoma beyond the bladder.

We report the case of a 61-year-old man, with a rare combination of two advanced urological tumors: a concomitant spread of an adenocarcinoma beyond the kidney and a urothelial carcinoma beyond the bladder. We simultaneously performed a primary curative prostatovesiculectomy and a nephroureterectomy on the right with ileal neobladder. To our knowledge, a case report of concomitant spread of an adenocarcinoma beyond the kidney (pT3 pN0 M0 G3) and a urothelial carcinoma beyond the bladder (pT3a pN0 M0 G3) with subsequent curative therapy has thus far not been published. A combination of the two diseases described here is obviously a remarkable rarity.

Carcinoma, Renal Cell↗
PubMed2000

Blastocyst-ET and monozygotic twinning.

PURPOSE: To examine the rate of monozygotic twinning associated with blastocyst transfer using commercially available, cell-free culture systems with unmanipulated blastocysts. METHODS: A retrospective analysis was conducted in multiple private and academic infertility centers throughout the United States, of 199 pregnant patients following in vitro fertilization (IVF) blastocyst embryo transfer (ET). Human embryos obtained through standard IVF stimulation protocols were cultured in commercially available, cell-free media systems and transferred as blastocysts. The main outcome measure was the rate of monozygotic twinning. RESULTS: A total of 199 blastocyst-ET pregnancies were achieved during the study period at the fertility centers examined. Monozygotic twinning was noted in 10/199 (5%) of these pregnancies. All were monochorionic diamnionic. CONCLUSIONS: Monozygotic twinning previously has been reported following IVF, especially in relation to assisted hatching. While blastocyst transfer has been available for many years using coculture, there have been no published multicenter reports of monozygotic twinning associated with unmanipulated blastocysts. In a multicenter analysis, a definite increase in monozygotic twinning was seen following blastocyst-ET. We believe this phenomenon is real and that this information should be considered when counseling patients for treatment.

Cell-Free System↗
PubMed2000

Ordinal knowledge: number names and number concepts in Chinese and English.

Previous research has demonstrated cross-language variation in early counting associated with linguistic differences in number-naming systems. Ordinal number names are typically learned later than cardinal names, but languages also differ in the regularity with which they form these names. Elementary school children in China and the U.S. showed differences in the acquisition and use of ordinal numbers corresponding to linguistic differences in ordinal names in their native languages. On tasks assessing children's conceptual knowledge of ordinal relations, a more complicated picture emerged. These results suggest that (a) children induce their language's set of ordinal number names by generalization based on rules sanctioned by early examples, and (b) the relation between ordinal names and ordinal concepts is a complex one, with language only one source of difficulty in understanding ordinal relations. Implications for studies of the relation between linguistic structure and cognitive development are discussed, in particular the possibility that effects of linguistic differences may vary for different levels of development and for different aspects of cognition.

Child↗
PubMed2000

Chronic graft-versus-host disease-related polymyositis as a cause of respiratory failure following allogeneic bone marrow transplant.

An unusual case of respiratory failure and dropped head syndrome as a complication of severe chronic graft-versus-host disease (GVHD)-related polymyositis is described. The patient required tracheostomy and mechanical ventilation but recovered following treatment with aggressive immunosuppression and intensive rehabilitation. The differential diagnoses of muscle weakness in the bone marrow transplant (BMT) patient and the dropped head syndrome are both discussed. To our knowledge, this is the first reported case of respiratory failure requiring mechanical ventilation occurring as a complication of GVHD-related polymyositis.

Adult↗