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Biomedical subjects

D C Miller

Publications and source records attributed to D C Miller.

At least 361 records · Page 20Linked to original sources

Is the quantum of transmitter release composed of subunits? A critical analysis in the mouse and frog.

1. Miniature end-plate potentials (m.e.p.p.s) were recorded from mouse diaphragm and frog cutaneous pectoris muscles and miniature end-plate currents (m.e.p.c.s) were recorded from frog cutaneous pectoris to investigate the proposal that the m.e.p.p. is built up of one to thirty subunits. Evidence for this hypothesis is drawn mainly from the observations that there is a class of m.e.p.p.s smaller than the classical m.e.p.p.s, and that histograms of m.e.p.p. amplitudes display multiple peaks which often appear to be regularly spaced and which extend throughout the histograms; in terms of the subunit hypothesis each successive peak results from an increasing integral number of subunits per m.e.p.p. (Kriebel, Llados & Matteson, 1976; Wernig & Stirner, 1977).2. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas confirmed the existence of two classes of m.e.p.p.s as reported by Kriebel & Gross (1974): a larger class (well described by a Gaussian curve) which consists of the classical m.e.p.p.s, and a smaller class with amplitudes considerable less than the classical m.e.p.p.s.3. Histograms of m.e.p.p. amplitudes and m.e.p.c. areas showed multiple peaks that extended throughout the histograms.4. Autocorrelations of the histograms, an unbiased method used to test for regularity in data, showed that the multiple peaks were not regularly spaced, as required by the subunit hypothesis.5. A series of computer simulations demonstrated that, for expected levels of base-line noise in the recording system, multiple peaks that extend throughout histograms of m.e.p.p. amplitudes could arise from subunits only if the standard deviation of the subunit amplitude were less than 2-5% of the mean subunit amplitude and the standard deviation of the variability in post-synaptic sensitivity were less than 2% of the mean post-synaptic sensitivity. It seems unlikely that the variability in post-synaptic sensitivity and in proposed subunit amplitude would be as small as this.6. Taking more realistic estimates for the standard deviation of the subunit amplitude of 12% of the mean subunit amplitude and standard deviation of the variation in post-synaptic sensitivity of 4% of the mean sensitivity, it was found that at most three to four regularly spaced peaks would be apparent in m.e.p.p. amplitude histograms due to subunits.7. On the basis of these theoretical considerations it seems doubtful that the multiple peaks observed to extend throughout histograms of m.e.p.p. amplitudes could arise from subunits; therefore, the experimental data that have been used to support the subunit hypothesis are unlikely to have arisen from a subunit mechanism.8. We suggest that there are few, if any, data that directly support the subunit hypothesis. The multiple peaks observed to extend throughout m.e.p.p. amplitude histograms most likely arise from random variation in the data, although additional factors cannot be ruled out.

Animals↗

Suicide, affective disorder, and women physicians.

Recent publications have noted a rate of suicide for women physicians considerably higher than that for women in the general population. The authors comment on some of the methodologic problems involved in this research and discuss the interaction between affective disorder and suicide as but a partial explanation of the higher risk of suicide among women physicians. The authors conclude that a number of risk factors are involved both in the relatively high lethality rate of some groups of professional women and in the relatively low lethality rate of women in general.

Adult↗

Spontaneous dissection of the ascending aorta diagnosed by two-dimensional echocardiography.

In two patients with acute dissection of the ascending aorta, the diagnosis was made with two-dimensional echocardiography and confirmed by aortography. The echocardiograms localized the intimal flap and false channel in both cases. Although clinical evaluation and indicated radiologic studies remain the primary modalities of diagnosis in acute aortic dissection, two-dimensional echocardiography may be a useful additional diagnostic technique.

Adult↗

Therapeutic efficacy of intraaortic balloon pump counterpulsation. Analysis with concurrent "control" subjects.

During a 7-year period, intraaortic balloon pumping (IABP) was attempted in 319 cardiac surgical patients. The indications for IABP were stringent and consisted of unsuccessful discontinuation of cardiopulmonary bypass (39%), anticipated failure (40%) to wean from cardiopulmonary bypass, postoperative low cardiac output, or intractable ventricular tachyarrhythmias (15%). IABP support was successfully instituted in 280 patients and was unsuccessful in 39 patients ("controls"). These two groups were comparable except for an older mean age and a higher ejection fraction in controls. Operative mortality rates were 45% and 62% for IABP and control groups, respectively (p = 0.077). This difference was most evident in coronary artery bypass patients, in whom the decision to institute IABP counterpulsation was made intraoperatively before attempted discontinuation of cardiopulmonary bypass. Two years postoperatively the actuarial survival rate was 45 +/- 3% for the IABP group and 23 +/- 9% for the control group (p = 0.006). After exclusion of operative deaths, however, these survival rates were 81 +/- 3% and 60 +/- 20%, respectively (p = NS). The average hospital charge incurred by IABP patients was threefold greater than that of uncomplicated cardiac surgical procedures. We conclude that IABP counterpulsation is therapeutic for some cardiac surgical patients, but its benefits cannot be defined easily. The long-term survival rates for patients with advanced disease requiring IABP support perioperatively are poor and warrant continued development of more effective methods of mechanical circulatory assistance and heart replacement.

Assisted Circulation↗

Discharges of Purkinje cells and mossy fibres in the cerebellar vermis of the monkey during saccadic eye movements and fixation.

1. Discharges of Purkinje cells and of presumed mossy fibres were extracellularly recorded from vermal lobules VI and VII of two monkeys during saccadic eye movements and fixation. Among the units showing changes in activity in relation to either saccades or eye position, eighty-four units were identified as mossy fibres and ninety-one units were Purkinje cells.2. Based on the discharge patterns associated with saccades, mossy fibre units were classified into long-lead burst, burst, and burst-tonic units. The long-lead burst units (twenty-eight units) started firing long before the saccades, the discharge consisting of a prelude (average lead time: 160 msec) and a burst (average lead time: 16 msec). In twenty-two units the saccade-related bursts showed a directional preference. The burst units (thirty-seven units) started firing slightly before the saccade onset (average lead time: 7.4 msec) and thirteen units showed directional preference. The bursts in burst-tonic units (thirteen units) had an average lead time of 0.2 msec.3. Among the ninety-one Purkinje cells, eighty-eight cells showed bursts associated with saccades. Three units paused for all directions of saccades.4. Seventy-one units out of the eighty-eight burst Purkinje cells showed bursts beginning approximately at the saccade onset (average lead time: 0.6 msec) and lasting throughout the saccade. The durations of bursts and saccades were highly correlated (correlation coefficients ranging from 0.70 to 0.88).5. In the remaining seventeen burst Purkinje cells, the bursts followed the saccade onset (average delay: 32 msec). The bursts started approximately 40 msec before the end of a saccade and persisted on the average 70 msec after its completion. Peak firing rate occurred with a close temporal relation to the end of the saccade.6. The tonic activity in nineteen mossy fibres and five Purkinje cells changed with eye positions. In the nineteen mossy fibres, there were thirteen burst-tonic and six tonic units. The activity in the five Purkinje cells was a linear function of horizontal eye position.

Action Potentials↗

Carotid back pressures in conjunction with cerebral angiography.

A method for obtaining carotid back pressures at the time of cerebral angiography is described. These preoperative measurements were compared to intraoperative measurements in 18 patients. Preoperative mean carotid back pressures (usually common carotid pressures) were obtained by occluding the artery with a double-lumen balloon catheter and recording the pressure distal to the balloon. Although the mean arterial blood pressure and the arterial carbon dioxide tension proved to be variables, the correlation of the pressures measured at angiography and at surgery was high (p less than 0.001).

Arteriosclerosis↗

Concomitant resection of ascending aortic aneurysm and replacement of the aortic valve: operative and long-term results with "conventional" techniques in ninety patients.

We reviewed a consecutive series of 90 patients undergoing concomitant resection of ascending aortic anerysm and aortic valve replacement (AVR) utilizing noncomposite "conventional" techniques in order to assess the early and late results, to define limitations of this operative approach, and thereby to clarify the indications for composite reconstruction of the aortic root. Mean age was 55 years. Twenty percent had Marfan's syndrome, and 13% had aortic dissections. The cause of the aneurysm was dissection in 13% of cases, syphilis in 11%, atherosclerosis in 9%, and degeneration (with or without cystic medionecrosis) in 67%. Follow-up averaged 3.8 years and extended to 11.5 years maximum. AVR and complete excision of the aneurysm (preserving small tongues of aortic wall circumscribing the coronary artery ostia) coupled with tubular graft replacement of the ascending aorta were performed. Nineteen percent of patients required individual technical modifications relating to the coronary arteries. Operative mortality rate was 13%, with the majority of deaths being due to cardiac causes. Contemporary (1975 to 1978) operative mortality rate was 4.3%. Seven percent required re-exploration for hemorrhage and 2.4% had perioperative myocardial infarctions. Late functional results were generally good (average N.Y.H.A. Class 1.4). Late thromboembolism, angina, myocardial infarction, and congestive heart failure occurred at linearized rates of 3.4% per patient-year, 4.9% per patient-year, 1.1% per patient-year, and 5.2% per patient-year, respectively. No prosthetic valve endocarditis, graft infection, or recurrent aneurysms of the aortic root were observed. Late reoperation was necessary in eight patients (3% per patient-year), but reoperation for disease confined to the ascending aorta accounted for only three of these cases (1.1% per patient-year). Overall actuarial survival rates were 67% +/- 5% at 5 years and 50% +/- 9% at 10 years; survival rates for the 78 operative survivors were 77% +/- 5% and 57% +/- 10% at the same time intervals, respectively. Only one late death could be attributed to complications arising in the reconstructed aortic root. These results confirm that such simple, noncomposite techniques are safe, portend minimal risk of late complications and the attendant necessity for reoperation, and provide satisfactory long-term survival. We believe that composite techniques should be primarily reserved for selected cases of advanced necrotizing prosthetic or natural endocarditis.

Adult↗

A surgical approach for S,L,L single ventricle incorporating total right atrium--pulmonary artery diversion.

Patients with single ventricle and unfavorable anatomy for partitioning procedures have been considered inoperable. Such was the case in two patients with single ventricle and subaortic inverted (hypoplastic) infundibulum associated with subaortic obstruction and levo-transposition of the great vessels (S,L,L). Both had undergone pulmonary artery banding in infancy and presented 11 and 14 years later, cyanotic and severely incapacitated. Both patients were treated surgically by resection of the subaortic obstruction, patch closure of the right artrioventricular valve, closure of the proximal pulmonary artery, and diversion of systemic venous flow through a xenograft valved conduit from the right atrium to the distal pulmonary artery. Early postoperative complications included atrial dysrhythmias and right-sided congestion. The first patient, who had massive cardiomegaly and complete heart block preoperatively, developed congestive failure 20 months postoperatively. The second patient has an excellent functional result and is leading a normal life 1 years after operation. This procedure may be of value for patients with single ventricle in whom corrective ventricular septation is considered too risky or technically unfeasible.

Adolescent↗

Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position.

Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

Aortic Valve↗

Pulmonary artery balloon counterpulsation for acute right ventricular failure.

The development and availability of right ventricular assist devices has not kept pace with the evolution of devices designed to mechanically support the systemic circulation. This report describes the application of the counterpulsation concept to the pulmonary circuit to unload the failing right ventricle and augment pulmonary blood flow. Conventional, widely available balloon pumping equipment was employed. Use of this double balloon pump system enabled a patient to be weaned from cardiopulmonary bypass after all other measures had failed. Other relevant potential clinical applications for this technique are discussed.

Assisted Circulation↗