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Biomedical subjects

C C Miller

Publications and source records attributed to C C Miller.

At least 19 recordsLinked to original sources
PubMed1999

Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.

BACKGROUND: Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable. METHODS: Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass. RESULTS: Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002). CONCLUSIONS: Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options.

Angina Pectoris↗
PubMed1999

Spinal cord protection in descending thoracic and thoracoabdominal aortic repair.

BACKGROUND: During simple cross-clamp repair of the descending thoracic or thoracoabdominal aorta, the likelihood of neurologic complications increases greatly after only 30 minutes of spinal cord ischemia. At greatest risk are patients with type II thoracoabdominal aortic aneurysms. METHODS: We reviewed our experience of simple cross-clamp repair and procedures accompanied by adjuncts, paying particular attention to the outcome of patients who had type II thoracoabdominal aortic aneurysms. Between February 1991 and March 1998, 508 patients had descending thoracic and thoracoabdominal aortic repair, 255 (50.2%) of whom received the adjuncts of cerebrospinal fluid drainage and distal aortic perfusion. RESULTS: Fifteen patients died on the day of operation and could not be evaluated for neurologic deficit. The overall incidence of neurologic deficit was 33 of 493 patients (6.7%). In patients who received adjuncts, neurologic deficit occurred in 9 of 247 (3.6%) overall; in types I and II it was 8 of 164 (4.9%), and in type II alone, 7 of 87 (8.1%). Neurologic deficit in simple cross-clamp patients was 24 of 246 (9.8%) overall; in types I and II it was 15 of 99 (15.2%), and in type II alone, 13 of 44 (29.6%). CONCLUSIONS: With the surgical adjuncts of cerebrospinal fluid drainage and distal aortic perfusion, the probability of neurologic deficit is lowered appreciably.

Adolescent↗
PubMed1999

The impact of diaphragm management on prolonged ventilator support after thoracoabdominal aortic repair.

PURPOSE: The relationship of the division of the diaphragm during thoracoabdominal aortic repair to prolonged ventilator support has not been studied. The purpose of this study was (1) to determine whether preservation of diaphragm integrity has a significant effect on postoperative ventilator duration and (2) to elucidate other pulmonary risk factors related to thoracoabdominal aortic surgery and to study the relationship of these factors to the intact diaphragm technique. METHODS: Between February 1991 and January 1997, we repaired 397 descending and thoracoabdominal aortic aneurysms. Descending thoracic aneurysms were not included in the study because their repair does not include the diaphragm. A total of 256 patients participated in this study. The diaphragm was divided in 150 patients and left intact in 106 patients. Examined as potential risk factors were patient demographics, history and physical findings, aneurysm extent, urgency of the procedure, acute dissection, cross-clamp time, homologous and autologous blood product consumption, and adjunctive operative techniques. FEV1 also was considered in the 197 patients for whom preoperative spirometry was available. Prolonged mechanical ventilation was defined as ventilator support for >72 hours. Data were analyzed by univariate contingency table and multiple logistic regression methods. RESULTS: Increasing age (odds ratio [OR], 1.02/y; P <.02), current smoking (OR, 2.6; P <.0008), total cross-clamp time (OR, 1.0/min; P <.008), units packed red blood cells transfused (OR, 1.06/unit; P <.008), and division of the diaphragm (OR, 2.03; P <.02) were significant, independent predictors of prolonged ventilation. Sixty-seven percent of patients (71 of 106) whose diaphragms were preserved were extubated in <72 hours compared with 52% of patients (78 of 150) who underwent diaphragm division (OR, 0.53; P <.02). CONCLUSION: Independently of well known pulmonary risk factors, an intact diaphragm during thoracoabdominal aortic repair results in a higher probability of early ventilator weaning.

Adolescent↗
PubMed1999

Mint2/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease.

Aberrant metabolism of the amyloid precursor protein (APP) is believed to be at least part of the pathogenic process in Alzheimer's disease. The carboxy-terminus of APP has been shown to interact with the Mint/X11 family of phosphotyrosine binding (PTB) domain-bearing proteins. It is via their PTB domains that the Mints/X11s bind to APP. Here we report the cloning of full-length mouse Mint2 and demonstrate that in primary cortical neurons, Mint2 and APP share highly similar distributions. Mint2 also colocalizes with APP in transfected CHO cells. In Mint2/APP-cotransfected cells, Mint2 reorganizes the subcellular distribution of APP and also increases the steady-state levels of APP. Finally, we demonstrate that Mint2 is associated with the neuritic plaques found in Alzheimer's disease but not with neurofibrillary tangles. These results are consistent with a role for Mint2 in APP metabolism and trafficking, and suggest a possible role for the Mints/X11s in the pathogenesis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Actual versus actuarial analysis for cardiac valve complications: the problem of competing risks.

Methods for analyzing rates of events such as heart valve failure following surgery are important for comparing different techniques and devices; however, in patients undergoing major surgery, other risks such as mortality compete with the risk of heart valve failure to determine each patient's final outcome. When multiple, mutually exclusive endpoints are possible, a situation known to statisticians as a competing risks problem arises. No single statistical technique that is currently available provides an entirely satisfactory solution to this problem. We argue that in order for valve failure incidences to be useful clinically, the overall patient outcome milieu from which these failures arise must be considered. In this article, we review recent work in the area of competing-risks analysis as it pertains to heart valve surgery outcome.

Actuarial Analysis↗
PubMed1998

Cyclin-dependent kinase-5 is associated with lipofuscin in motor neurones in amyotrophic lateral sclerosis.

We have studied the distribution of cyclin dependent kinase-5 (cdk-5) within spinal cord in sporadic and two superoxide dismutase type 1 (SOD1) familial cases of amyotrophic lateral sclerosis (ALS). Although most neurofilament accumulations in ALS motor neurones did not appear to contain high levels of cdk-5, intense cdk-5 immunoreactivity was observed in perikarya of degenerating neurones in many ALS cases. Here, cdk-5 co-localised with lipofuscin. Co-localisation of cdk-5 with lipofuscin was also observed in some aged non-affected controls although this labelling was less intense than the ALS cases. The biogenesis of lipofuscin is believed to be linked to oxidative stress and oxidative stress and free radical damage have been suggested to be part of the pathogenic process of ALS, possibly involving apoptotic mechanisms. cdk-5 has recently been associated with apoptosis. These observations suggest a role for cdk-5 in the pathogenesis of ALS.

Adult↗
PubMed1998

Preoperative cardiac evaluation is unnecessary in most patients undergoing vascular operations.

BACKGROUND: This study evaluated the impact of Goldman's index (GI), radionuclide ventriculography (RVG), and dipyridamole-thallium scintigraphy (DTS) on predicting cardiac outcome after vascular operations. METHODS: A total of 463 consecutive patients undergoing vascular operations were divided into those who had no DTS, those who had reversible ischemia by DTS, and those who had no reversible ischemia by DTS. GI, ejection fraction, wall motion abnormalities, rate of coronary angiography, and revascularization were determined for each group. RESULTS: Coronary revascularization was ultimately performed in 8% of patients with no DTS, 7% of patients with no ischemia by DTS, and 9% of patients with ischemia by DTS. The GI of 6.1 in patients who died postoperatively was significantly higher than the GI of 3.6 in patients who survived (P = 0.02). RVG did not predict mortality, morbidity, or need for coronary revascularization. CONCLUSION: Clinical assessment remains a good predictor for cardiac outcome in patients undergoing vascular operations. More extensive cardiac testing should be reserved for patients with higher GI and active cardiac problems.

Aged↗
PubMed1998

Operation for acute and chronic aortic dissection: recent outcome with regard to neurologic deficit and early death.

BACKGROUND: We reviewed our experience in the repair of acute and chronic aortic dissection with regard to early neurologic deficit and death. METHODS: Between February 1991 and June 1996, we performed 206 operations on 195 patients for aortic dissection. Ascending or arch repair, or a combination (type A dissection) was performed on 92 of 206 patients (45%); 44 of 92 (48%) were acute dissection and 48 of 92 (52%) were chronic. Descending or thoracoabdominal repair (type B dissection) was performed on 114 of 206 patients (55%); 22 of 114 (19%) were acute and 92 of 114 (81%) were chronic. RESULTS: Among type A cases, strokes occurred in 6 of 92 patients (7%) overall; 4 of 44 (9%) were acute cases and 2 of 48 (4%) were chronic (p < 0.34). Early deaths for type A were 11 of 92 (12%) overall; 9 of 44 (20%) acute and 2 of 48 (4%) chronic (p < 0.02). In type B cases, neurologic complications were 15 of 114 (13%) overall; 7 of 22 (32%) were acute cases and 8 of 92 (9%) were chronic (p < 0.004). Early deaths for type B were 12 of 114 (11%) overall; 3 of 22 (14%) acute and 9 of 92 (10%) chronic (p < 0.6). Preoperative hypotension was significant in acute type A patients, with strokes in 2 of 7 (29%) hypotensives compared with 2 of 37 (5%) normotensives (p < 0.05) and early death in 4 of 7 (57%) hypotensives versus 5 of 37 (14%) normotensives (p < 0.009). CONCLUSIONS: Morbidity and mortality for repair of chronic dissection types A and B were acceptable. Preoperative hypotension in acute type A dissection was a major predisposing factor toward stroke (29% versus 5%, p < 0.05). Acute type B dissection had acceptable mortality (14%) but a high rate of neurologic complications (32%).

Acute Disease↗
PubMed1998

Effect of extended cross-clamp time during thoracoabdominal aortic aneurysm repair.

BACKGROUND: In previous studies of the neurologic outcome of patients undergoing thoracoabdominal aortic aneurysm repair with the simple cross-clamp technique, cross-clamp time of greater than 30 minutes was identified as an important risk factor. We retrospectively examined the effect of clamp time of 30 minutes or greater on outcome for patients undergoing repair with the addition of surgical adjuncts. METHODS: Between February 1991 and June 1996 we operated on 370 patients for thoracoabdominal or descending thoracic aortic aneurysm. Two hundred seventy-one of these patients with cross-clamp times of 30 minutes or greater were included in this study. One hundred twelve patients underwent simple cross-clamp repair, whereas 159 were operated on with the surgical adjuncts of distal aortic perfusion and cerebrospinal fluid drainage. RESULTS: By multivariate analysis, acute dissection, surgical adjuncts, and aneurysm extent proved most significant in overall patient outcome. The overall rate of early neurologic deficits was 23 of 271 (8.5%). For highest risk patients with type II thoracoabdominal aortic aneurysms, the rate of neurologic deficits was 11 of 29 (38%) for cross-clamp versus 6 of 82 (7.3%) for adjunct operation patients (odds ratio = 0.13; p < 0.001). CONCLUSIONS: The adjuncts of cerebrospinal fluid drainage and distal aortic perfusion decreased the risk of extended cross-clamp time during thoracoabdominal aortic aneurysm repair, particularly for highest risk type II.

Aged↗
PubMed1998

Management of the patient with aortic root disease and aortic insufficiency.

There is no single standardized method of repair for the anatomic variations in aortic root pathology, which may include dissection, aneurysmal dilation, and valve disease and can occur at the annulus, sinuses of Valsalva, or the sinotubular junction. Composite valve/graft replacement, valve resuspension, and allograft each play a significant role in aortic root therapy, but none is applicable in all cases. Patient age, Marfan's syndrome, endocarditis, and previous valve replacement are examples of some of the wide variations in delineating factors.

Aorta↗
PubMed1998

Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of the chest incision.

PURPOSE: Although some authors advocate hypothermic circulatory arrest for spinal cord protection in descending thoracic and thoracoabdominal repair, this method has been associated with high morbidity and mortality rates in other studies. The safety and effectiveness of this surgical adjunct were evaluated. METHODS: Between February 1991 and April 1997, 409 patients underwent thoracic or thoracoabdominal aortic repair. Because of an inability to gain proximal aortic control because of anatomic or technical difficulty, hypothermic circulatory arrest was used in 21 patients (4.9%). Thirteen patients were men, 8 were women, and the median age was 57 (range, 21 to 81 years). Four patients (19%) had Marfan's syndrome, and 1 had aortitis. Seven patients (33%) had aortic dissection (4 chronic type A, 2 chronic type B, 1 acute B), and 1 had aortic laceration. All but 6 patients had hypertension. Fifteen patients (73%) were operated on for repair of the distal arch and descending thoracic aorta, 4 (19%) for repair of the distal arch and thoracoabdominal aorta, and 2 for repair of either the thoracoabdominal or descending thoracic aorta alone. Surgery for 9 patients (43%) also included bypass grafts to the subclavian or innominate arteries. Six operations (29%) were urgent. RESULTS: The overall 30-day mortality rate was 29% (6 of 21 patients). Among urgent patients, the mortality rate was 50% (3 of 6 patients) versus 20% (3 of 15) for elective patients. Of the remaining 15 patients, renal failure occurred in 1 (7%) and heart failure in 2 (13%). Ten patients (67%) had pulmonary complications. Encephalopathy occurred in 5 patients (33%) and stroke in 2 (13%), and spinal cord neurologic deficit developed in 2 (13%). The median recovery was 28 days (range, 10 to 157 days). CONCLUSION: Hypothermic circulatory arrest did not reduce the incidence of deaths and morbidity to a rate comparable with our conventional methods. We recommend the judicious application of this method in rare instances when proximal control is not feasible or catastrophic intraoperative bleeding leave the surgeon with no other option.

Adult↗
PubMed1998

Importance of intercostal artery reattachment during thoracoabdominal aortic aneurysm repair.

PURPOSE: We studied the relationship of neurologic deficit to ligation, reimplantation, and preexisting occlusion of intercostal arteries to determine which arteries and consequent management are most critical to outcome in thoracoabdominal aortic aneurysm repair. METHODS: From February 1991 to July 1996, 343 patients with thoracoabdominal aortic aneurysms underwent repair by one surgeon. In this study, only Crawford types I, II, and III (n = 264) were considered. Of these, 110 (42%) were type I, 116 (44%) type II, and 38 (14%) type III. The adjuncts of distal aortic perfusion and cerebrospinal fluid drainage were used in 164 patients (62%). Data were analyzed by contingency table and by multiple logistic regression. RESULTS: Early neurologic deficit occurred in 23 patients (8.7%), and late deficit in 10 patients (3.8%). Neurologic deficit in patients with at least one reimplantation and no ligation of arteries T11 or T12 occurred in 19 of 147 (12.9%). Neurologic deficit for occlusion of the same arteries occurred in 11 of 111 (9.9%), whereas for ligation of T11 and T12 neurologic deficit occurred in three of six (50%; reimplantation, p < 0.03; occlusion, p < 0.006). In addition, reimplantation of intercostal arteries T9 or T10 was significantly associated with reduced late neurologic deficit in multivariate analysis (p = 0.05). No other intercostal artery status was associated with modification of the neurologic deficit rate. Multivariate analysis showed type II aneurysms and acute dissections to be significantly associated with an increased risk of postoperative neurologic deficit (p < 0.0009, 0.002, respectively). Adjuncts were protective (p < 0.007), most often in types II and III (14.1% neurologic deficit in type II with adjunct, 35.3% without; 0% in type III with adjunct, 20% without). CONCLUSION: Patients with patent arteries at the T11/T12 level have highly variable outcomes depending on whether the arteries are reattached or ligated. Our data suggest that reimplantation of thoracic intercostal arteries T11 and T12 is indicated when these arteries are patent. Reimplantation of T9 and T10 lowers the risk of late neurologic deficit, probably by decreasing the spinal cord's vulnerability to changes in blood and cerebrospinal fluid pressure in the days after surgery. Adjuncts lower overall risk and provide adequate time for targeted intercostal artery reimplantation.

Adolescent↗
PubMed1998

Impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair.

PURPOSE: We examined the impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair. METHODS: Between January 1991 and July 1996, 367 patients underwent thoracoabdominal and descending thoracic aortic repair. Baseline and postoperative total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, fibrinogen, prothrombin time (PT), and partial thromboplastin time (PTT) were measured for 286 patients. We examined the impact of distal aortic and direct visceral perfusion on liver function-related clinical laboratory values. Univariate and multivariate statistical methods for categorical and continuous variables were used. RESULTS: In categorical analysis, type II thoracoabdominal aortic aneurysm, history of hepatitis, and emergency presentation had a statistically significant multivariate association with abnormal laboratory values. In continuous-distributed multivariate data analysis, type II thoracoabdominal aortic aneurysm and visceral perfusion were statistically significant predictors of postoperative alkaline phosphatase, PT, and PTT. Type II aneurysms increased postoperative liver function-related laboratory values significantly above other aneurysm types (alkaline phosphatase, +114 IU, p < 0.0001; PT, +1.99 seconds, p < 0.02; PTT, +6.7 seconds, p < 0.03). Visceral perfusion was associated with a concomitant decrease (alkaline phosphatase, -101.2 IU, p < 0.0001; PT, -1.8 seconds, p < 0.07; PTT, -5.6 seconds, p < 0.02). CONCLUSIONS: Visceral perfusion negates the rise in postoperative liver function-related clinical laboratory values associated with type II thoracoabdominal aortic aneurysm repair.

Alkaline Phosphatase↗
PubMed1998

Spinal cord protection in descending thoracic and thoracoabdominal aortic aneurysm repair.

During aneurysm repair of the descending thoracic or thoracoabdominal aorta, the likelihood of neurological complications increases greatly after only 30 minutes of spinal cord ischemia. However, the manifestation of paraplegia or paraparesis relates not only to aortic cross-clamping time, but to multiple factors that may include aortic dissection, previous aortic surgery, advanced age, preoperative renal insufficiency, rupture, and most significantly, aneurysm extent. At greatest risk is the patient with type II thoracoabdominal aortic aneurysm. For this patient the simple cross-clamp technique, which uses no protective surgical adjuncts, heightens the threat of neurological deficit. With the surgical adjuncts of cerebrospinal fluid drainage and distal aortic perfusion, the probability of neurological deficit is appreciably lowered.

Aortic Aneurysm, Abdominal↗
PubMed1998

Cyclin D2 interacts with cdk-5 and modulates cellular cdk-5/p35 activity.

Cyclin-dependent kinase-5 (cdk-5) is a serine/threonine kinase that displays neurone-specific activity. Experimental manipulation of cdk-5 expression in neurones has shown that cdk-5 is essential for proper development of the nervous system and, in particular, for outgrowth of neurites. Such observations suggest that cdk-5 activity must be tightly controlled during development of the nervous system. To identify possible regulators of cdk-5, we used the yeast two-hybrid system to search for proteins that interact with cdk-5. In two independent yeast transformation events, cyclin D2 interacted with cdk-5. Immunoprecipitation experiments confirmed that cyclin D2 and cdk-5 interact in mammalian cells. Cyclin D2 did not activate cdk-5 as assayed using three different substrates, which was in contrast to a known cdk-5 activator, p35. However, cyclin D2 expression led to a decrease in cdk-5/p35 activity in transfected cells. As cyclin D2 and cdk-5 are known to share overlapping patterns of expression during development of the CNS, the results presented here suggest a role for cyclin D2 in modulating cdk-5 activity in postmitotic developing neurones.

Animals↗
PubMed1998

Neuropathological abnormalities in transgenic mice harbouring a phosphorylation mutant neurofilament transgene.

Ser55 within the head domain of neurofilament light chain (NF-L) is a target for phosphorylation by protein kinase A. To understand further the physiological role(s) of NF-L Ser55 phosphorylation, we generated transgenic mice with a mutant NF-L transgene in which Ser55 was mutated to Asp so as to mimic permanent phosphorylation. Two lines of NF-L(Asp) mice were created and these animals express the transgene in many neurones of the central and peripheral nervous systems. Both transgenic lines display identical, early onset, and robust pathological changes in the brain. These involve the formation of NF-L(Asp)-containing perikaryal neurofilament inclusion bodies and the development of swollen Purkinje cell axons. Development of these pathologies was rapid and fully established in mice as young as 4 weeks of age. The two transgenic lines show no elevation of NF-L, neurofilament middle chain (NF-M), or neurofilament heavy chain (NF-H), and transgenic NF-L(Asp) represents only a minor proportion of total NF-L protein. Because other published transgenic lines expressing higher levels of wild-type NF-L do not exhibit phenotypic changes that in any way resemble those in the NF-L(Asp) mice and because the two different NF-L(Asp) transgenic lines display identical neuropathological changes, it is likely that the pathological alterations observed in the NF-L(Asp) mice are the result of properties of the mutant NF-L. These results support the notion that phosphorylation of Ser55 is a mechanism for regulating neurofilament organisation in vivo.

Amino Acid Substitution↗