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Biomedical subjects

D C Miller

Publications and source records attributed to D C Miller.

At least 235 records · Page 13Linked to original sources

Effects of hypothermia on testicular ischemia.

The ischemic effects of prolonged testicular torsion have been well documented; however, prevention or arrest of the damaging effects of prolonged ischemia has been incompletely studied. Two groups of Sprague-Dawley rats were subjected to varying lengths of bilateral testicular ischemia. Group I underwent normothermic ischemia for two, four, and six hours. Likewise, Group II underwent similar time periods of ischemia, however, after thirty minutes of normothermic ischemia the scrotum of each animal was placed into an ice bath maintained at 4C. Two weeks postoperatively, bilateral orchiectomy was performed. Histology of the testes of the two groups was compared. Neither group revealed significant destruction of the germinal epithelium after two hours of ischemia. Group I revealed only 25% preservation of the germinal epithelium at four hours and only 8% preservation at six hours of ischemia. In contrast, Group II which received ice showed 90% preservation of germinal epithelium at four hours and 85% preservation at six hours of ischemia. We conclude that external ice application significantly preserves seminiferous tubules at four and six hours of ischemic injury in the rat testicle.

Animals↗

Treatment of patients with aortic dissection presenting with peripheral vascular complications.

The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients.

Adolescent↗

Clinically atypical expression of pathologically typical Lewy-body parkinsonism.

Six patients autopsied by the neuropathology service at UMDNJ-Robert Wood Johnson Medical School between 1985 and 1988 had pathologically typical Lewy-body Parkinson's disease (PD). Review of their clinical records revealed that none had clinically typical PD. Atypical clinical features included juvenile onset, retrocollis, strong family history, and absence of tremor, flexed posture, or levodopa response. One patient had dementia without parkinsonism. We conclude that the clinical spectrum of Lewy-body PD is wider than is generally assumed and that the diagnosis of pathologically typical Parkinson's disease cannot be excluded on clinical grounds alone.

Adult↗

Intraoperative echocardiography and Doppler color flow mapping in freehand allograft aortic valve and root replacement.

Intraoperative epicardial echocardiography and color flow Doppler were performed before and after cardiopulmonary bypass in 17 consecutive patients undergoing 20 freehand allograft aortic valve replacements. Native aortic valves were replaced in 12, and prostheses in 8 patients. Precardiopulmonary bypass echocardiography estimates of annular diameter guided allograft selection and predicted length of allograft aortic root required, defined coronary situs, and revealed other cardiac abnormalities. These included unanticipated severe mitral regurgitation (which precluded allograft aortic valve replacements in one patient), left-to-right shunts in the membranous septum, ascending aortic dissection, and aortic root pathology requiring coronary reimplantation or bypass. Postcardiopulmonary bypass echocardiography demonstrated acceptable competency of 18/19 allograft valves (mild or no aortic insufficiency), and successful repair of 3/4 shunts. Mild mitral regurgitation was detected more often at postcardiopulmonary bypass than precardiopulmonary bypass (15 vs 11 cases) and postcardiopulmonary bypass estimates of mitral regurgitation severity corollated well with subsequent postoperative follow-up. IOE allows selection and thawing of the allograft valves prior to aortic cross clamping, minimizing cross-clamp time. It detects important concomitant cardiac abnormalities, and predicts postoperative allograft valve and mitral competency. Intraoperative echocardiography Doppler, is therefore, a useful adjunct for allograft aortic valve replacements or aortic root replacement.

Adolescent↗

Predictors of outcome in patients with prosthetic valve endocarditis (PVE) and potential advantages of homograft aortic root replacement for prosthetic ascending aortic valve-graft infections.

Seventy-five surgically treated patients with prosthetic valve endocarditis were treated at the Stanford University Medical Center. This was a multivariate analysis analyzing both patient related factors, bacteriology, and surgical findings. The conclusions among 10 patients with allograft valves, 20% had an annular abscess; this occurred in 36% of 29 patients with porcine valves, and 65% of these with mechanical prosthesis. Though prevention, again, is key in this especially devastating disease, once infection has been established and an aggressive approach is indicated, it would appear that a homograft re-replacement or free aortic homograft valve replacement can deal with severe tissue destruction to prevent recurrence.

Abscess↗

Multiple system degeneration with glutamate dehydrogenase deficiency: pathology and biochemistry.

The neuropathological findings in a patient with antemortem diagnosis of olivopontocerebellar atrophy (OPCA) and reduced leucocytic glutamate dehydrogenase (GDH) activity included cerebellar cortical degeneration, most marked in the superior vermis, mild atrophy of the pons and the inferior olivary nucleus, marked reduction of anterior horn cells at all levels and gliosis in both lateral columns. GDH activities and their thermolability in "soluble" and "particulate" fractions in the cerebral cortex, cerebellar hemisphere and vermis were not significantly different from the values in two control brains. GDH mRNA in the patient's brain was not altered in size or amount.

Aged↗

Determinants of survival and left ventricular performance after mitral valve replacement. Department of Veterans Affairs Cooperative Study on Valvular Heart Disease.

To determine how survival and clinical status were related to left ventricular (LV) size and systolic function after mitral valve replacement, 104 patients (48 mitral regurgitation [MR], 33 mitral stenosis [MS], and 23 MS/MR) with isolated mitral valve replacement were evaluated before and after surgery. Preoperative hemodynamic abnormalities by cardiac catheterization were improved 6 months after surgery in all three patient groups. The patients with MR exhibited reductions in LV end-diastolic volume index (EDVI) (117 +/- 51 to 89 +/- 27 ml/m2, p less than 0.001) and ejection fraction (EF) (0.56 +/- 0.15 to 0.45 +/- 0.13, p less than 0.001); however, the ratio of forward stroke volume to end-diastolic volume increased (0.32 +/- 0.21 to 0.45 +/- 0.17, p less than 0.001) because of the elimination of regurgitant volume. Survival analysis revealed that mortality was significantly higher in MS or MS/MR patients with postoperative EDVI more than 101 ml/m2 (p less than 0.001 and p less than 0.042, respectively) and in MR patients with postoperative EF less than or equal to 0.50 (p less than 0.031). Also, the majority of patients with MR or MS/MR and postoperative EDVI more than 101 ml/m2 and EF less than or equal to 0.50 were in New York Heart Association class III or IV. Multivariate logistic regression analysis in the patients with MR revealed that the strongest predictor of postoperative EF was preoperative EF (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Three-dimensional left ventricular midwall dynamics in the transplanted human heart.

To quantify the three-dimensional regional dynamics of the left ventricular (LV) midwall and the centroid and cross-sectional shape of the LV chamber in the transplanted human heart, 12 miniature radiopaque tantalum markers were implanted in the LV midwall of the donor heart at the time of cardiac transplantation in 15 patients. Stereo cineradiography in the late postoperative period (mean, 52 days after surgery) allowed computer-aided measurements of the three-dimensional coordinates of multiple sites in anterior, inferior, lateral, and septal LV regions at 16.7-msec intervals throughout the cardiac cycle. In awake, supine patients, from maximum to minimum LV volume, group mean translations of free wall markers ranged from 0.80 to 1.24 cm, directed toward the LV interior, whereas translations of septal wall markers were significantly less, 0.46 and 0.34 cm (p less than 0.01), directed away from the LV interior. A component of this translation along the septal-lateral axis was also significantly less (p less than 0.01) in the septum (0.19 and 0.20 cm) than in the free wall, where it ranged from 0.32 to 0.97 cm. The LV cross section was not circular, and anterior-inferior dimensions (7.18 +/- 0.66 and 6.13 +/- 0.79 cm, at maximum and minimum volumes, respectively) were significantly greater (p less than 0.01) than septal-lateral dimensions (5.78 +/- 0.65 and 5.12 +/- 0.48 cm), yielding an unchanging transverse elliptical LV eccentricity (0.58 +/- 0.13). The position of the LV center of volume did not change significantly from maximum to minimum volume in the direction of either the LV long axis or the anterior-inferior axis, but it did change significantly (0.55 +/- 0.23 cm, p less than 0.01) along the septal-lateral axis. We conclude 1) as viewed in a fixed external reference system, midwall sites in the interventricular septum of the transplanted human heart move paradoxically yet are relatively immobile compared with the three-dimensional dynamics of midwall sites in the LV free wall; 2) the transverse cross-sectional shape of the LV in the transplanted human heart is decidedly oval, with significantly greater anterior-posterior than septal-lateral dimensions at the time of maximum and minimum LV volumes; and 3) the center of volume in the transplanted human LV is remarkably stable in the directions of the LV long axis and anterior-posterior axis, suggesting a balance of forces along these axes, yet it moves significantly toward the interventricular septum, presumably counterbalancing the opposite translation during systole of the right ventricular (RV) center of volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Volume↗

Comparison of medical and surgical therapy for uncomplicated descending aortic dissection.

To guide the choice of medical versus surgical therapy for patients with descending (type B) aortic dissection (tear in the descending aorta without involvement of the ascending aorta), multivariate survival analysis was applied to 136 patients admitted to two medical centers between 1975 and 1988 with acute (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients; group 2, 106 patients without rupture, pulse loss, or visceral organ compromise; and group 3, 56 patients from group 2 without major cardiac or renal disease (23 surgical and 33 medical). Group 3 medical and surgical subgroups were well matched for baseline characteristics and were potential candidates for either mode of therapy. By Cox model analysis, significant predictors of mortality were pleural rupture, other dissection complications, increasing age, and cardiac disease (all p less than 0.01). Surgical versus medical therapy was not an independent determinant of survival in any of the three groups for acute or chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and 10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical). Despite the limitations of this retrospective study (including the possibility of undefined treatment selection biases), these data suggest that medical or early surgical therapy is associated with equivalent outcome in selected patients with uncomplicated acute or chronic descending aortic dissection.

Adrenergic beta-Antagonists↗

Differences in Hancock and Carpentier-Edwards porcine xenograft aortic valve hemodynamics. Effect of valve size.

We prospectively compared the hemodynamic performance of Hancock and Carpentier-Edwards bioprosthetic aortic valves in a randomized study of 100 patients. A total of 47 patients received the Hancock valve, and 53 received the Carpentier-Edwards valve. Mean pressure gradients were measured using micromanometer catheters and cardiac outputs by thermodilution. Multiple measurements were made in each patient with atrial pacing, volume infusion, and inotropic drugs for a total of 319 observations. The pressure gradients and Gorlin valve areas showed significant scatter caused by both flow-dependent and patient-dependent variability. Mean transvalvular pressure gradients were therefore compared after adjustment for flow rate and for random interpatient differences using analysis of variance and covariance. Pressure gradients were lower and Gorlin valve areas larger for the Hancock valve than for the Carpentier-Edwards valve, but the differences were significant only for the smaller valve sizes. Compared with the Carpentier-Edwards valve, the mean pressure gradients were significantly lower for the Hancock 19-mm modified orifice (MO) valves (16.9 versus 31.7 mm Hg, p = 0.04), for the 21-mm valves (15.2 versus 22.4 mm Hg, p = 0.003), and for the 23-mm MO valve (9.2 versus 13.8 mm Hg, p = 0.04). The Gorlin areas were also significantly larger for the Hancock 19-mm MO valve (0.85 versus 0.77 cm2, p = 0.004) and the 21-mm MO valve (1.11 versus 0.89 cm2, p = 0.0009) but not for the 23-mm MO valve (1.59 versus 1.14, p = 0.08). Mean gradients and valve areas were not different for any of the larger valve sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Hemodynamic comparison of Hancock and Carpentier-Edwards mitral bioprosthetic valves.

Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow-dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis↗

Importance of the mitral subvalvular apparatus for left ventricular segmental systolic mechanics.

The relative importance of the anterolateral (ANTLAT) and posteromedial (POSTMED) papillary muscle (PM) chordae tendineae for left ventricular (LV) segmental wall function was assessed in 12 in situ ejecting canine hearts. Pairs of piezoelectric crystals were placed in the regions subtending PM insertions and the ANTLAT LV free wall to measure wall thickness. After mitral valve replacement with complete preservation of the subvalvular apparatus, chordal attachments to either the ANTLAT PM or POSTMED PM were randomly severed using exteriorized snares, followed by subsequent division of the remaining chordae tendineae. Segmental wall function in each region was determined at each stage by segmental preload recruitable stroke work (sPRSW, slope of the segmental stroke work-end-diastolic wall thickness relation). The order in which the chordae were severed was unimportant (p greater than 0.530 in all regions). When the ANTLAT PM chordae were severed first, there were significant declines in sPRSW without a change in the wall thickness intercept in both the ANTLAT (-71.0 +/- 18.3 vs. -57.7 +/- 16.8 mmHg, p less than 0.05) and POSTMED (-81.8 +/- 23.1 vs. -65.4 +/- 17.3 mmHg, p less than 0.05) PM insertion sites. No further significant reductions in sPRSW in either region were detected after severing the remaining chordal attachments to the POSTMED PM. sPRSW in the ANTLAT LV free wall decreased progressively, reaching statistical significance when both sets of chordae tendineae were divided (-88.3 +/- 14.3 vs. -74.0 +/- 15.2 mm Hg, p less than 0.05). When the POSTMED PM chordae were severed first, no significant changes in sPRSW or the wall thickness intercept in either region of PM insertion were detected. Subsequent division of the ANTLAT PM chordal attachments reduced sPRSW significantly in both the ANTLAT PM (-65.9 +/- 21.1 vs. -56.1 +/- 22.1 mm Hg, p less than 0.05) and POSTMED PM (-78.8 +/- 24.7 vs. -67.2 +/- 24.0 mm Hg, p less than 0.05) insertion sites, without a shift in the wall thickness intercept. In the ANTLAT LV free wall, sPRSW again fell progressively, achieving statistical significance only when both chordal attachments were severed (-78.6 +/- 14.8 vs. -62.2 +/- 13.7 mm Hg, p less than 0.05). In conclusion, division of the chordae tendineae resulted in a decline in segmental LV function not only in the areas subtending PM insertions but also in remote LV regions. Furthermore, the influence of the ANTLAT PM chordae predominated local LV systolic function at both PM insertion sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The reversibility of canine vein-graft arterialization.

We assessed the reversibility of functional and morphological changes of arterialized vein segments by returning them to the venous circulation. Thirteen dogs underwent right carotid and femoral veno-arterial grafting. After 12 weeks, veno-arterial grafts were removed for contractility (norepinephrine [NE] and 5-hydroxytryptamine [5-HT]), luminal prostacyclin (PGI2), and morphometric analyses; the remaining segments were used as left jugular and femoral veno-venous grafts. After another 12 weeks, the veno-venous grafts were harvested. To NE, veno-arterial grafts (ED50, 5.4 +/- 0.1 [-log M]) were less sensitive than control veins (ED50, 6.0 +/- 0.2) or veno-venous grafts (ED50, 6.4 +/- 0.2) but were more sensitive than control arteries (ED50, 4.0 +/- 0.1); the maximum tension of veno-arterial grafts (6.2 +/- 0.6 g) was greater than that of veins, less than that of arteries (9.8 +/- 1.0 g), and comparable with that of veno-venous grafts (5.1 +/- 1.1 g). To 5-HT, veno-arterial (ED50, 7.5 +/- 0.1) and veno-venous (ED50, 7.3 +/- 0.2) grafts were more sensitive than arteries (ED50, 6.0 +/- 0.3), while the vein was unresponsive; the maximum tension of veno-arterial grafts (5.0 +/- 0.7 g) was less than that of arteries (6.9 +/- 0.9 g) and greater than that of veno-venous grafts (1.4 +/- 0.3 g). PGI2 production in veins (3.6 +/- 0.8 ng/ml), veno-arterial grafts (3.9 +/- 0.8 ng/ml), and veno-venous grafts (3.3 +/- 0.9 ng/ml) was comparable and less than that of arteries (6.4 +/- 0.9 ng/ml). Veno-arterial graft intimal thickness (127 +/- 8 microns) and intimal area (15.6 +/- 1.8 x 10(3) microns 2) tended to be greater than that in the veno-venous graft (113 +/- 9 microns and 12.4 +/- 1.8 x 10(3) microns 2); also, the veno-arterial graft medial area (103.0 +/- 7.3 x 10(3) microns 2) was greater than that of the veno-venous graft (80.3 +/- 6.9 x 10(3) microns 2), thereby resulting in a similar relative intimal area (13 +/- 1%). Therefore, some changes associated with arterialization, for example, adrenergic sensitivity, maximum tension to 5-HT, medial thickening, and perhaps intimal hyperplasia, reverted toward venous values when replaced in the venous environment, possibly due to variations in pressure, flow, shear stress, and/or graft preparation techniques. Luminal PGI2 was unchanged in the grafts, implying that graft contractility was not modulated by luminal PGI2.

Animals↗

Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism.

A 42-year-old woman suffered unexplained weight loss followed by action tremor and difficulty initiating gait. Three months after onset of symptoms, infiltrating ductal carcinoma of the breast, metastatic to liver and lymph nodes, was diagnosed and treated briefly with cyclophosphamide, methotrexate, and 5-flourouracil (5FU). Severe symmetric action and postural tremor with a myoclonic component developed, with minimal rest tremor, severe dysarthria and dysphagia, small-stepped and slightly ataxic gait progressing to a bedbound state, and severe widespread dystonic posturing. The latter began as a typical parkinsonian posture of trunk and upper extremities and progressed to a fixed and painful flexion of the elbows and wrists and extension of fingers and neck. Sinemet, anticholinergics, baclofen, diazepam, and plasmapheresis gave no benefit. The patient died of complications of immobility 5 months after neurologic symptom onset. Autopsy revealed many pigment-laden macrophages in substantia nigra and moderate loss of pigmented neurons. Inflammation, Lewy bodies, and tumor were absent. Cerebellar Purkinje cells were moderately depleted. Mild neuronal loss and gliosis were present in globus pallidus and cerebellar cortex. Stains for anti-human IgG, IgM, kappa, and lambda were negative. This, to our knowledge, is the first report of paraneoplastic degeneration of substantia nigra or paraneoplastic parkinsonism.

Adult↗