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Biomedical subjects

D C Miller

Publications and source records attributed to D C Miller.

At least 145 records · Page 8Linked to original sources

Pregnancy and bioprostheses: influence on structural valve deterioration.

The long-term performance of bioprostheses was evaluated in women 35 years of age or less to determine the influence of pregnancy on structural valve deterioration. Between 1972 and 1992, 237 female patients received 255 biological prostheses. Of the total operations, 53 were performed in patients who experienced pregnancy (P) and 202 in patients who were never pregnant (nonpregnant [NP]). The mean age of the P group was 23.0 +/- 5.8 years (standard deviation) (12 to 34 years) and of the NP group it was 27.1 +/- 6.3 years (8 to 35 years) (p < 0.05). The mean follow-up for the NP group was 6.8 years and for the P group it was 7.9 years. The late mortality was 2.26%/patient-year overall, 2.71%/patient-year for the NP group and 0.89%/patient-year for the P group (p = not significant [NS]). The P group of 52 patients had 94 pregnancies: 70 deliveries (74.5%) and 24 abortions (25.5%) (therapeutic, 14 [15%]). There were a total of 143 valve-related complications (P, 35; NP, 108); the majority for structural valve deterioration (SVD) 43% (109 patients), P 51% (27 patients) and NP 41% (82 patients) (p = NS). The valve-related reoperation rate paralleled the SVD rate at 42% (107 patients), P 51% (27 patients) and NP 40% (80 patients) (p = NS). The overall reoperative mortality rate was 6.0%. The interval from initial implant to reoperation was 99.6 +/- 3.6 months (p = NS groups P and NP).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Endovascular stent-grafting after arch aneurysm repair using the "elephant trunk".

A 68-year-old woman with severe chronic obstructive pulmonary disease, aortic valvular insufficiency, and diffuse thoracic aortic aneurysm underwent aortic valve replacement and separate Dacron graft replacement of the ascending aortic and arch aneurysms using the elephant trunk technique. She was discharged on the tenth postoperative day. Five months later, she underwent endovascular stent-graft repair of the descending thoracic aortic aneurysm. She recovered uneventfully, and was discharged on the third postoperative day. Follow-up computed tomography at 6 months demonstrated exclusion of all flow into the descending thoracic aortic aneurysm. The elephant trunk technique followed by endovascular stent-grafting of the descending thoracic component is a potential therapeutic option in selected high-risk patients with diffuse aortic aneurysmal disease.

Aged↗

Exploring better methods to preserve the chordae tendineae during mitral valve replacement.

BACKGROUND: It is not known how best to resuspend the mitral chordae tendineae during mitral valve replacement to optimize postoperative left ventricular (LV) systolic and diastolic function. METHODS: Six different techniques to preserve the chordae during mitral valve replacement were compared in 12 dogs using a nondistorting isovolumic technique: conventional, all chordae severed; anterior, all chordae preserved anteriorly; partial, anterior papillary muscle chordae preserved anteriorly; posterior, all chordae preserved posteriorly; oblique, anterior papillary muscle chordae directed anteriorly and posterior papillary muscle chordae posteriorly; and counter, opposite of oblique chordal direction. Control measurements (no chordal tension) were recorded between each experimental condition. RESULTS: The oblique method tended to have the best LV systolic function versus the conventional method (Emax = 4.0 +/- 1.8 versus 3.3 +/- 1.2 mm Hg/mL [mean +/- standard deviation]; p = 0.08 by repeated-measures analysis of variance; physiologic intercept Ees100 = 20.3 +/- 8.6 mL [p < 0.05 versus control]), with no major change in LV diastolic stiffness. The posterior method had a lower Emax (3.3 +/- 1.2 mm Hg/mL) than the oblique method, but a similar Ees100 (20.8 +/-8.1 mL; p < 0.05 versus control) and the best diastolic LV performance (LV diastolic stiffness = 0.46 +/- 0.23 mm Hg/mL). The counter method also had good systolic function (Emax = 3.8 +/- 1.2 mm Hg/mL; Ees100 = 19.7 +/- 7.5 mL; p < 0.05 versus control), but had less favorable diastolic properties (0.65 +/- 0.37 mm Hg/mL; p < 0.05 by repeated-measures analysis of variance versus posterior). CONCLUSIONS: In this isovolumic preparation in normal canine hearts, the oblique method of chordal resuspension was associated with the best LV systolic function, whereas the counter technique impaired LV diastolic function. These preliminary results warrant further study in ejecting and failing hearts to determine conclusively which chordal orientation best preserves LV performance after mitral valve replacement.

Animals↗

A method to assess endocardial regional longitudinal curvature of the left ventricle.

Knowledge of the instantaneous geometry of the left ventricular (LV) chamber is necessary to calculate LV function and wall stresses. We describe a method utilizing myocardial markers that does not rely on any a priori assumptions of global LV geometry. Five dogs underwent placement of 25 endocardial and 3 epicardial miniature LV markers. Six weeks later, the animals were studied during conscious closed-chest conditions. The three-dimensional coordinates of the LV markers were used to compute longitudinal fitted curves for LV walls and septum during steady-state conditions; endocardial radii of curvature (rcurv) were then computed for each region at the midequatorial (rcurv-eq) and apical levels. There was a uniform decrease in rcurv in each LV wall during systole (compared with diastole, P < 0.01); at end systole, rcurv was regionally heterogeneous between opposing walls, e.g., anterior and posterior rcurv-eq values were 17.2 +/- 2.0 and 17.7 +/- 1.8 (SD) cm, respectively (P < 0.05). At end diastole, only septal-lateral rcurv-eq was different (16.9 +/- 2.1 vs. 18.7 +/- 1.3 cm: P < 0.05). Normalization of rcurv (to instantaneous LV volume) removed the systolic-diastolic differences, but a similar pattern of regional heterogeneity persisted. The data presented pertain to the LV endocardial surface, but the method described can be applied to the epicardial surface as well; this new method offers promise in assessing dynamic changes in longitudinal LV endocardial curvature.

Analysis of Variance↗

Hypothalamic hamartoma and the Pallister-Hall syndrome.

The Pallister-Hall syndrome (PHS) was initially described as the congenital hypothalamic 'hamartoblastoma' syndrome in 1980. Cardinal manifestations of the syndrome consist of a hypothalamic hamartoma and extracranial abnormalities, initially thought to be fatal in the perinatal period. The original pathologic description of these hypothalamic lesions were from infants who died in the perinatal period and revealed small cells of variable density which resembled primitive undifferentiated germinal cells and appeared to invade the hypothalamic nuclei, suggesting a neoplastic potential. Hypothalamic lesions have now been removed from older infants and children with this syndrome and reveal a more mature histologic appearance typical of a hypothalamic hamartoma. We present 2 new cases of PHS who underwent surgery and demonstrate the maturational nature of the hypothalamic lesion and the phenotypic variability of the syndrome.

Abnormalities, Multiple↗

Recombinant bovine somatotropin increases milk yield and calf gain in diverse breeds of beef cattle: associated changes in hormones and indices of metabolism.

In Exp. 1, Angus (A, n = 30), Charolais (C, n = 37), and Simmental (S, n = 30) multiparous cows received (s.c.) recombinantly derived bovine somatotropin (bST; sometribove, 500 mg) or vehicle (VEH) at 2-wk intervals from 124 to 228 d postpartum (DPP). Calves were weaned at 228 DPP. Bovine somatotropin increased (P < .01) milk yield and percentage of milk fat similarly in A, C, and S cows. Calf weaning weight was greater (P < .05) in cows treated with bST than in those given VEH. Administration of bST decreased deposition of fat and increased concentrations of IGF-I, insulin, glucose, and nonesterified fatty acids. In Exp. 2, we compared effects of bST initiated before or after the breeding season. Charolais (n = 33) and S (n = 40) cows were administered (at 2-wk intervals) VEH or bST beginning at 28 DPP (B-bST) or bST beginning at 105 DPP (A-bST). Calves were weaned at 243 DPP. Administration of bST before or after the breeding season increased milk yield on DPP 136 and 194; however, yields were greater in A-bST than in B-bST cows. Milk yields were similar in all cows at 236 DPP, corresponding to decreased forage availability. Calf body weight was greater (P < .05) in A-bST than VEH; B-bST calves were similar to VEH. Fat depth was greater in VEH than in bST-treated cows in C but not in S cows. Serum IGF-I was greater in A- and B-bST than in VEH cows. Mean days from calving to serum progesterone > 1 ng/mL and pregnancy rates were similar in VEH, A-, and B-bST cows. Administration of bST increased cow milk yield and subsequent calf weaning weight when initiated after 100 d postpartum. As anticipated, bST increased IGF-I, insulin, glucose, and nonesterified fatty acids. Administration of bST before and during the breeding season did not affect reproductive performance.

Animals↗

The hippocampus in aging and Alzheimer's disease.

The role of imaging in the evaluation of neurodegenerative disorders is summarized. The primary role of imaging is to exclude potentially treatable disorders such as meningioma, extracerebral hematoma, Wernicke's disease, and hypothyroidism. Atrophic changes dominate in the hippocampal region on Alzheimer's disease versus the anterior, frontal, and temporal lobes in Pick's disease. Signal hypointensity in the putamen on T2-weighted spin-echo images favors poorly drug-responsive Parkinson's disease whereas putaminal hyperintensity is observed with Creutzfeldt-Jacob, Wilson's, and Leigh's diseases. As our population ages, a thorough understanding of imaging findings in a geriatric population assumes an increasing importance.

Aged↗

A Gly1127Ser mutation in an EGF-like domain of the fibrillin-1 gene is a risk factor for ascending aortic aneurysm and dissection.

Ascending aortic disease, ranging from mild aortic root enlargement to aneurysm and/or dissection, has been identified in 10 individuals of a kindred, none of whom had classical Marfan syndrome (MFS). Single-strand conformation analysis of the entire fibrillin-1 (FBN1) cDNA of an affected family member revealed a G-to-A transition at nucleotide 3379, predicting a Gly1127Ser substitution. The glycine in this position is highly conserved in EGF-like domains of FBN1 and other proteins. This mutation was present in 9 of 10 affected family members and in 1 young unaffected member but was not found in other unaffected members, in 168 chromosomes from normal controls, and in 188 chromosomes from other individuals with MFS or related phenotypes. FBN1 intragenic marker haplotypes ruled out the possibility that the other allele played a significant role in modulating the phenotype in this family. Pulse-chase studies revealed normal fibrillin synthesis but reduced fibrillin deposition into the extracellular matrix in cultured fibroblasts from a Gly1127Ser carrier. We postulate that the Gly1127Ser FBN1 mutation is responsible for reduced matrix deposition. We suggest that mutations such as this one may disrupt EGF-like domain folding less drastically than do substitutions of cysteine or of other amino acids important for calcium-binding that cause classical MFS. The Gly1127Ser mutation, therefore, produces a mild form of autosomal dominantly inherited weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection later in life.

Adult↗

Transluminal placement of endovascular stent-grafts for the treatment of descending thoracic aortic aneurysms.

BACKGROUND: The usual treatment for thoracic aortic aneurysms is surgical replacement with a prosthetic graft, but the associated morbidity and mortality are considerable. We studied the use of transluminally placed endovascular stent-graft devices as an alternative to surgical repair. METHODS: We evaluated the feasibility, safety, and effectiveness of transluminally placed stent-graft to treat descending thoracic aortic aneurysms in 13 patients over a 24-month period. Atherosclerotic, anastomotic, and post-traumatic true or false aneurysms and aortic dissections were treated. The mean diameter of the aneurysms was 6.1 cm (range, 5 to 8). The endovascular stent-grafts were custom-designed for each patient and were constructed of self-expanding stainless-steel stents covered with woven Dacron grafts. RESULTS: Endovascular placement of the stent-graft prosthesis was successful in all patients. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent-graft in 12 patients, and partial thrombosis in 1. Two patients initially had small, residual patent proximal tracts into the aneurysm sac, but both tracts thrombosed within two months after the procedure. In four patients, two prostheses were required to bridge the aneurysm adequately. There have been no deaths or instances of paraplegia, stroke, distal embolization, or infection during an average follow-up of 11.6 months. One patient with an extensive chronic aortic dissection required open surgical graft replacement four months later because of progressive dilatation of the arch. CONCLUSIONS: These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation.

Adult↗

Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989.

BACKGROUND: Primary central nervous system non-Hodgkin's lymphoma (NHL-CNS) is an enigmatic disease of uncertain origin. At the Massachusetts General Hospital, 104 patients with NHL-CNS were seen from 1958 through 1989. An impression of changes in the frequency of diagnosis, character of the tumors, and therapy for this disease prompted this study of the pathologic features, clinical data, and natural history of this tumor in these 104 patients. METHODS: Histologic slides (neurosurgical specimens and autopsy tissues) were available for 99 patients. The tumors were classified by the Working Formulation classification. Immunostaining data and all clinical data were retrieved from the relevant offices and hospital charts. RESULTS: Primary central nervous system non-Hodgkin's lymphoma tripled in frequency (5.66 cases per year in 1978-89 versus 1.75 cases per year in 1958-77) and now represents 6.6% of all primary brain neoplasms (versus 3.3% before 1978; chi 2 = 17.52, P < 0.01). For the 99 tumors histologically classified, 89% were high grade. Intermediate grade lymphomas, once the second most common subtype, have disappeared since 1983. All tumors had diffuse architecture; 77% (including all 11 patients with acquired immune deficiency syndrome) were large cell subtypes. Two cases were intravascular lymphoma. With one exception, all of the 41 tumors evaluated were B-cell types; 32 of 40 had monotypic surface immunoglobulin. There was 1 T-cell lymphoma. Of 64 tumor recurrences, 29 were at the initially defined site; 12 were in the leptomeninges, 29 were in other sites in the neuraxis, and 8 were in systemic sites. Systemic metastases have not occurred since 1984. Median survival for the 68 patients who survived after diagnostic surgery and for whom follow-up information could be obtained was 19 months; 9 months for those with high grade tumors and 30.5 months for those with intermediate grade tumors. This difference was not significant (P = 0.13). A separate set of seven patients had focal tumorlike lymphoid infiltrates composed of benign-appearing lymphocytes, which were associated with good long term survival. The differential histologic diagnosis of NHL-CNS was occasionally difficult, and the spectrum of this differential was broader than generally stated. CONCLUSIONS: Primary central nervous system non-Hodgkin's lymphoma has increased in frequency even in nonimunocompromised patient populations. This increase has been accompanied by the disappearance of intermediate grade histologic types, suggesting a fundamental shift in the biology of the neoplasms. The introduction of chemotherapeutic regimens appears to have altered the natural history such that systemic metastases outside the central nervous system no longer occur, and there are now some long term survivors of this formerly uniformly fatal disease.

Brain Neoplasms↗

Experimental evaluation of different chordal preservation methods during mitral valve replacement.

During chordal-sparing mitral valve replacement (MVR), some recommend anatomic reattachment of the anterior leaflet chordae to the anterior annulus; others advocate shifting the chordae to the posterior annulus. To compare the results of these techniques with those of conventional MVR (total chordal excision), 21 dogs were studied 5 to 12 days after implantation of tantalum markers to measure left ventricular volume and geometry. One to 3 weeks later, animals underwent conventional MVR (n = 7) or chordal-sparing MVR with either anterior chordal reattachment (n = 7) or posterior transposition (n = 7). Contractility was assessed using physiologic volume intercepts for end-systolic elastance, preload recruitable stroke work, and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume. The physiologic intercept for end-systolic elastance did not change after anterior or posterior MVR, but increased from 60 +/- 14 mL before MVR to 72 +/- 17 mL with conventional MVR (p < 0.002), indicating impaired left ventricular contractility. Similarly, the physiologic intercept for preload recruitable stroke work and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume increased 22% +/- 13% and 28% +/- 13%, respectively, after conventional MVR, but neither changed after anterior or posterior MVR. Although the end-diastolic pressure-volume relationship did not change with either chordal-sparing technique, its slope increased 98% +/- 73% after conventional MVR (p < 0.008). Thus, although chordal preservation maintained better systolic and diastolic function, there was no substantial difference between the results of the anterior and posterior chordal-sparing techniques in this model.

Animals↗

Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass.

Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tracheal intubation without neuromuscular block in children.

We have studied 80 healthy children, aged 2-14 yr, undergoing adenotonsillectomy in a double-blind, randomized design. Tracheal intubation facilitated by either suxamethonium 1.5 mg kg-1 or alfentanil 15 micrograms kg-1 was compared after induction of anaesthesia with propofol 3-4 mg kg-1. The quality of tracheal intubation was graded according to the ease of laryngoscopy, position of the vocal cords, coughing, jaw relaxation and movement of limbs. There were no significant differences in the overall assessment of intubating conditions between the two groups, and all children underwent successful tracheal intubation. Fewer patients coughed (P < 0.014) and limb movement was less common (P < 0.007) after tracheal intubation facilitated by suxamethonium. Alfentanil attenuated the haemodynamic responses to tracheal intubation.

Adenoidectomy↗

Evaluation of myocardial motion tracking with cine-phase contrast magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The accuracy of myocardial motion measurements, computed from cine-phase contrast (cine-PC) magnetic resonance (MR) velocity data, was compared with directly visualized motion of MR signal voids caused by implanted tantalum markers in anesthetized dogs. METHODS: Magnetic resonance imaging (MRI) data were electrocardiogram-gated and divided into 16 phases per cardiac cycle. Myocardial trajectories as a function of time in the cardiac cycle were measured using both methods for four to seven markers in each of eight animals. RESULTS: The peak observed in-plane excursion was 4.0 +/- 2.1 mm. The average deviation between displacements derived from velocity data versus displacements visualized directly was 1.1 +/- 0.7 mm (27.5% of the peak displacement). The difference was less if three separate MR scans were used to measure each velocity component in the cine-PC method. This improvement is probably caused by improved temporal resolution. CONCLUSIONS: Cine-PC MRI offers a noninvasive method for accurate quantification of myocardial motion.

Animals↗

Aortic cobwebs: an anatomic marker identifying the false lumen in aortic dissection--imaging and pathologic correlation.

PURPOSE: To describe and estimate the frequency of fibroelastic cords or bands projecting from the false lumen wall ("aortic cobwebs") in acute and chronic dissections. MATERIALS AND METHODS: Pathologic specimens (n = 23), routine magnetic resonance (MR) images (n = 27), and intravascular (n = 5) and transesophageal (n = 3) ultrasound (US) images from 43 patients with aortic dissection were reviewed, and the presence and configuration of cobwebs were noted. RESULTS: Aortic cobwebs usually bridge the junction of the dissection flap with the outer wall of the false lumen (the line of dissection) but occasionally project like small tendrils from the false lumen wall remote from the line of dissection. Cobwebs were found in 17 of 23 pathologic specimens and on six of 27 MR images, two of five intravascular US scans, and one of three transesophageal US scans. CONCLUSION: Aortic cobwebs most likely represent residual ribbons of media that have been incompletely sheared from the aortic wall during the dissection process. As such, they can serve as an anatomic marker of the false lumen. They are occasionally seen on routine aortic images and may, therefore, prove useful for orientation during percutaneous or surgical interventional procedures to relieve ischemic complications of aortic dissection.

Aortic Dissection↗

Left atrial pressure-clamp servomechanism demonstrates LV suction in canine hearts with normal mitral valves.

A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling.

Animals↗