Self-assembled nanofiber hydrogels for mechanoresponsive therapeutic anti-TNFα antibody delivery.

Low molecular weight hydrogels, prepared from glycosyl-nucleoside-lipid amphiphiles, exhibit shear-thinning behaviour and reversible thermally- and mechanically-triggered sol-gel transitions. Using mechanical shear stimulation, the release of entrapped anti-TNFα increases and the released anti-TNFα demonstrates efficacy in in vitro neutralization bioassays. Delivery of anti-TNFα is of general interest and broad medicinal utility for treating autoimmune diseases such as rheumatoid arthritis.

Propranolol therapy in patients undergoing myocardial revascularization.

The records of 185 consecutive patients having myocardial revascularization were reviewed with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Tachycardia and hypertension before cardiopulmonary bypass were slightly more common in patients never taking propranolol or those who had discontinued it for more than 48 hours before operation. There was no statistically significant difference in the incidence of postbypass hypotension among patients who took propranolol within 24 hours of operation, those who discontinued it more than 24 hours before operation, and those who never took the drug. Operative mortality was not significantly different among patients who received propranolol within 48 hours of operation (3%), those who never took it and those who discontinued it more than 48 hours before operation (4%). Early in the series, five patients had an acute myocardial infarction within 48 hours after routine preoperative withdrawal of propranolol. Because complete withdrawal of propranolol in patients with unstable angina pectoris may lead to acute myocardial infarction, we recommend gradual withdrawal of the drug during 48 hours before operation. If this is not possible because anginal pain recurs or intensifies, then reduced doses may be given safely up to 10 hours before revascularization, provided that the patient is a satisfactory candidate for bypass and that adequate myocardial revascularization can be accomplished.

Value of coronary bypass surgery. Controversies in cardiology: Part I.

The value of coronary bypass surgery has been studied carefully during the last decade. Four methods, none perfect, have been used to compare the results of such surgery with the results of medical therapy. New data are likely to be merely supportive rather than the outcome of a definitive study with a new and a acceptable experimental design. It is therefore time to analyze the available data in light of the treacherousness of the disease and to determine if a clear trend is evident. There appears to be sufficient evidence to state that properly performed coronary bypass surgery will increase coronary blood flow and relieve angina pectoris in 90 percent of patients; total relief of angina can be expected in 60 percent and partial relief in 30 percent. Compared with modern medical therapy, properly performed coronary bypass surgery appears to prolong the life of patients who have obstruction of the left main coronary artery or triple or double vessel disease. There is not adequate evidence to state that the procedure will prolong the life of patients with single vessel obstruction. However, patients with single vessel obstruction and unacceptable angina pectoris should be considered for bypass surgery (especially patients with obstruction of the left anterior descending coronary artery). In practice, at Emory University Hospital, Atlanta, bypass surgery is recommended for young people with few symptoms if compelling obstructing lesions are present and in older patients only if their symptoms require it. Medical therapy is given before and after bypass surgery. When bypass surgery is performed in an excellent fashion (operative risk 1 percent) a great deal of "controversy" about this problem vanishes.

Vasodilator therapy during coronary artery surgery. Comparison of nitroglycerin and nitroprusside.

Intraoperative hypertension is a common problem in patients undergoing myocardial revascularization. Twenty patients who developed acute hypertension after sternotomy were studied. Ten patients received three doses of intravenous nitroglycerin (32, 64, and 96 mcg. per minute), and 10 patients received nitroprusside, (20, 40, and 60 mcg. per minute). All patients were anesthetized with morphine, diazepam, nitrous oxide, oxygen, and pancuronium bromide. Five patients in each group also received enflurane. The study compared the effects of nitroglycerin and nitroprusside on systemic hemodynamics, myocardial oxygen supply/demand relationships, and ischemic changes on the electrocardiogram. Both drugs decreased preload and afterload in a dose-related manner. Heart rate increased significantly only with the largest dose of each drug. Myocardial oxygen demand was decreased significantly by both drugs, while the coronary perfusion pressure was decreased more by nitroprusside. Both nitroglycerin and nitroprusside improved left ventricular performance. Nitroglycerin improved ST-segment depression in eight of 10 patients; while nitroprusside improved the ST segments in six patients, and worsened the ST segments in three patients. None of the nitroglycerin group had worsening of the electrocardiographic ST segments. These findings demonstrate that both drugs can control intraoperative hypertension and can decrease myocardial oxygen demand. Nitroglycerin was shown to improve ischemic changes on the electrocardiogram more often than nitroprusside.

Pretreatment with lidoflazine, a calcium-channel blocker. Useful adjunct to heterogeneous cold potassium cardioplegia.

Ten mongrel dogs were studied to determine if pretreatment with lidoflazine would protect the canine myocardium during aortic cross-clamping when circumflex coronary artery occlusion limits the distribution of cold potassium cardioplegia. A canine right heart bypass preparation was used. Regional function was determined with a sonomicrometer. Twenty minutes before aortic cross-clamping, lidoflazine or solvent was administered in a random, blind fashion. A circumflex artery snare prevented the cardioplegic solution from entering the circumflex artery. A 100 minute arrest period with cardioplegic infusion every 20 minutes was followed by 45 minutes of reperfusion before global and regional function were reevaluated. In the group receiving solvent, postarrest function in the circumflex region recovered to only 30% of prearrest values (p less than 0.05), a marked functional deterioration. In the group protected by lidoflazine, function in the circumflex region returned to 90% of prearrest values (NS). Function in the left anterior descending (LAD) regions of both groups demonstrated full recovery after arrest. Global left ventricular function was well preserved in both groups and failed to reflect the damaged, malfunctioning region in the group receiving solvent. These findings suggest that pretreatment with lidoflazine can improve myocardial protection when delivery of cardioplegia is not homogeneous.

Autologous blood transfusion during cardiac surgery. A re-evaluation of three methods.

The use of autologous blood transfusion to decrease blood bank requirements and improve coagulation parameters during cardiac surgery is still controversial. This study was undertaken to re-evaluate three methods of autologous blood transfusion. Before bypass, 13 to 15 percent of the patient's estimated blood volume was removed and stored with either CPD or heparin at room temperature and returned via a peripheral vein after bypass. All patients had significant abnormalities in their PTT, PT, and platelet counts after bypass. Heparinized autologous blood removed from the vena cava cannula was the only technique which significantly improved the PTT and platelet count. Total blood bank requirements were significantly less for the autologous blood groups than for controls. There was a saving of 18 percent in banked blood requirements. Fresh frozen plasma and platelets were not found to be routinely needed during cardiac surgery.

The spectrum of left main coronary artery disease: variables affecting patient selection, management, and death.

A total of 178 patients having a diagnosis of left main coronary artery stenosis were divided into three groups as follows: surgical, Group I (n = 135 patients); operable medically treated, Group II (n = 21 patients); and inoperable, Group III (n = 22 patients). Groups 1 and 2 were comparable with regard to clinical profile, extent of anatomic coronary disease, and left ventricular function. Inoperable patients had a much higher incidence of prior myocardial infarction (especially anterior), more severe distal coronary disease, and markedly depressed left ventricular function. The hospital mortality rate for surgical patients was 4% (6/135). The late mortality rate, (median follow-up = 23.4 months) was 7% (9/135). For operable patients, the late mortality rate was 43% (9/21) at 28 months. In the inoperable group, the late death rate at 20 months was 59% (13/22). Actuarial survival at 24 months for the three groups was: 88%, 66%, and 42%, respectively. Of the nine patients who died in the operable group, two had less than 75% obstruction of the left main coronary artery and two had normal left ventricular wall motion. Although patients with higher grades of left main coronary artery stenosis and reduced left ventricular function are at greater risk, patients with less obstruction and good left ventricular function are also at risk and should have myocardial revascularization with some sense of urgency. The population of left main coronary artery stenosis is a heterogeneous one, and comparison of surgical versus medical therapy should exclude inoperable patients. The operative mortality rate has been greatly reduced in recent years (2% in the last 100 cases); this is attributed to careful monitoring in the critical prebypass period, aggressive pharmacologic treatment of increased preload, tachycardia, and hypertension, and improved aurgical technique, with emphasis on careful myocardial preservation. Adherence to these principles makes frequent use of the intra-aortic balloon either before or after revascularization unnecessary.

Open heart surgery in patients in the eighth and ninth decades of life.

One hundred fifty-one patients aged 70-89 years underwent a variety of open heart surgical procedures during a period of 1 year. We divided these patients into two groups: Group A was comprised of 127 patients between 70 and 79 years of age. In group B, 24 patients were between 80 and 89 years of age. These patients underwent elective open heart surgery. Information was retrieved retrospectively from the computerized data pool of the cardiothoracic registry in our institution. Statistical analysis in these two groups revealed no significant differences in any of the evaluated factors. We concluded that age should not be a contraindication for cardiac operations.

Verapamil and myocardial preservation in patients undergoing coronary artery bypass surgery.

The value of verapamil hydrochloride as a myocardial preservative when administered prior to or during periods of myocardial ischemia was studied in patients with normal preoperative cardiac function during elective coronary artery bypass grafting. Myocardial protection included systemic hypothermia (28 degrees C) and hypothermic hyperkalemic cardioplegia. Patients were randomly divided into four groups. Group 1 received intravenous administration of verapamil prior to aortic cross-clamping. Group 2 received intravenous verapamil plus verapamil in the cardioplegic solution. Group 3 received verapamil in the cardioplegic solution only. Group 4 was given no verapamil. Oxygen extraction during the reperfusion period was greatest in Group 4. However, the incidence of pacing was 50 to 78% in Groups 2 and 3, who were given verapamil in the cardioplegic solution. These groups also had a greater need for inotropic agents for discontinuation of cardiopulmonary bypass (CPB). This study indicates that verapamil may be a useful pretreatment prior to CPB and ischemia, but is not effective and may even be detrimental when administered during ischemic periods to patients with good myocardial function.

Criteria for operability and reduction of surgical mortality in patients with severe left ventricular ischemia and dysfunction.

A series of 188 patients who were operated on for left ventricular ischemia and dysfunction is presented. Angina was a prominent symptom in all patients, and a history of congestive heart failure could be elicited in 20%. Mean ejection fraction for the series was 0.35, with 67% having an ejection fraction of 0.35 or less 24%, 0.20 or less. Complete revascularization was accomplished whenever possible; more than 70% of the patients had triple-vessel disease, and single bypass was performed infrequently (5%). Factors thought to be important in achieving a low operative mortality (2.1%) were: precise prebypass monitoring, particularly with the V5 precordial lead; maintaining a low rate-pressure product (less than 12,000) prior to bypass; myocardial preservation with cold hyperkalemic or hyperkalemic-hyperosmolar solution; and careful titration of inotropic and vasodilator drugs. Inotropic drugs and intraaortic balloon pumping were used frequently in this series. The late mortality was 4.3%. Angina was completely relieved or improved in 94% of the patients. Those having a history of congestive heart failure had an increased late mortality rate, four times that of the entire series.

The role of nicardipine during anesthesia and surgery.

The stresses of the perioperative period often requires the use of vasoactive drugs for hemodynamic control. Nicardipine hydrochloride is a short-acting dihydropyridine calcium antagonist with a unique configuration and characteristics that make it attractive for intraoperative and postoperative use. Nicardipine has highly specific modes of action, producing coronary and systemic vasodilation, a reduction in coronary spasm, and cardioprotection not consistently seen with other calcium antagonists. It produces a rapid decrease in blood pressure without severe hypotension, sinus arrest, cardiac depression, or clinically significant tachycardia, while it increases myocardial contractility and cardiac output. Nicardipine dilates the cerebral vasculature but does not significantly increase cerebrospinal fluid pressure in surgical patients without intracranial lesions. Unlike nifedipine, which must be administered orally or sublingually, nicardipine is stable in parenteral formulation ("light stable and water soluble") and can be given intravenously. The distinctive characteristics of nicardipine suggest that anesthesiologists might find it preferable to other vasodilators or calcium antagonists for hemodynamic control during and after surgery.

Hemodynamic effects of verapamil during fentanyl-nitrous oxide anesthesia.

The hemodynamic effects of a verapamil infusion were investigated in six dogs given fentanyl-nitrous oxide anesthesia. Verapamil, 0.2 mg/kg, was given followed by an infusion of 3, 6, and 9 micrograms/kg per minute, which produced plasma verapamil concentrations ranging from 98 to 204 ng/ml. Verapamil significantly reduced the systemic vascular resistance index and mean arterial pressure. The decrease in afterload led to an increase in cardiac index, since there was little change in myocardial contractility (LV dP/dt). Administration of calcium chloride, 20 mg/kg, did not reverse the hemodynamic effects of verapamil. The data indicate that in dogs verapamil can be given, even in high concentrations, during fentanyl-nitrous oxide anesthesia without serious adverse electrophysiologic or hemodynamic consequences.

Sensitivity to conversational deviance in right-hemisphere-damaged patients.

To participate meaningfully in conversation, speakers must be sensitive to statements which advance and those which block the direction of a discourse. The effect of right-hemisphere damage (RHD) on sensitivity to conversational advancers and blockers was investigated by asking subjects to interpret normal conversations and conversations which were blocked by violations of Gricean maxims: specifically, tangential and redundant statements. Results indicate that RHD patients function normally in canonical, directed conversation. However, they have difficulty interpreting and judging the effect of blocking statements, particularly with regard to tangentiality. The results are discussed in terms of a mental model of directed conversation which incorporates both structural and affective components.

The effects of right hemisphere damage on the pragmatic interpretation of conversational remarks.

The ability to interpret conversational utterances was assessed in a group of 12 male patients with unilateral right hemisphere brain damage (RHD) and 12 non-brain-damaged, age-matched male control subjects. Subjects listened to short vignettes which described both the affective tone of the relationship between a speaker and an actor, and the actor's performance on a task. Each vignette concluded with the speaker characterizing the actor's performance. In half of the items, the speaker's utterance was literally true; in the other half, the utterance was literally false and invited a nonliteral interpretation. Results showed no appreciable differences in the performance of control subjects and RHD patients when interpreting literally true utterances. In contrast, the two groups differed reliably when interpreting the pragmatic intent of nonliteral utterances: Control subjects used information about both the actor's performance and the speaker-actor relationship, while RHD patients demonstrated difficulty in using the information about the speaker-actor relationship. Results have implications for patients' understanding of essential elements of conversations, such as characters' internal states and their intentions in employing different forms of literal and nonliteral language.

Story processing in right-hemisphere brain-damaged patients.

The understanding of stories requires sensitivity to structural aspects of narrative, the emotional content conveyed by the narrative, and the interaction between structural and emotional facets of the story. Right-hemisphere-damaged (RHD) and normal control subjects performed a number of different analytic tasks which probed their competence at story comprehension. Results revealed that RHD subjects perform at a level comparable to that of normal controls with stories that follow a canonical form and that they show few difficulties with structural aspects of narrative. Contrary to expectation, they are strongly influenced by the "interest" level of a story and by other factors that tap emotional sensitivity. Findings are discussed in terms of the processing and arousal mechanisms which may give rise to the observed pattern of difficulties in RHD patients.

Delayed fatal hemothorax due to traumatic carotid dissection: a case report of a previously unreported cause of death.

A unique case of delayed fatal hemothorax in a 12-year-old girl resulting from atypical dissection of a traumatic carotid aneurysm is reported, due to occult neck trauma received in a sledding accident which occurred one week prior to death. Aspects of traumatic carotid dissection and forensic implications of delayed presentation of such findings in the setting of occult trauma are discussed.

"Hyperacute" subdural hematoma: CT mimic of recurrent episodes of bleeding in the setting of child abuse.

Mixed density extraaxial hematomae on computed tomography (CT) scanning generally represent recurrent episodes of bleeding (chronic subdural hematoma with rebleeding). Hyperacute hemorrhages in which the patient is actively bleeding or has a coagulopathy have also been described as mixed density. We report a case of child abuse in a fourteen month old child who presented with a CT scan showing a mixed density subdural hematoma which was originally interpreted as recurrent episodes of hemorrhage, but who had evidence of only acute, active bleeding at surgery and by histologic examination. There is a proportionally high incidence of subdural hematoma in cases of child abuse, due in part to the increased susceptibility of the immature brain to trauma. Because the mechanism of injury is different for hemorrhage due to hyperacute subdural hematoma (SDH) and that of acute bleeding within a chronic SDH, the distinction between these entities has potentially important legal implications in cases of suspected child abuse. This potential pitfall in interpretation of the CT scan has not to our knowledge been reported in the forensic literature.

Comparative hemodynamic effects of labetalol and hydralazine in the treatment of postoperative hypertension.

The antihypertensive efficacy and safety of IV labetalol were evaluated and compared with the efficacy and safety of IV hydralazine in the treatment of postoperative hypertension. Twenty patients undergoing major noncardiac surgery were entered into the study. Patients were randomized and treated for postoperative hypertension with either labetalol (n = 10) or hydralazine (n = 10). Labetalol and hydralazine both produced significant reductions in arterial blood pressure (p less than 0.001) within 10 minutes, which lasted at least 2 hours. In addition, labetalol produced a significant reduction in the heart rate and rate-pressure product without creating any adverse effects. In contrast, hydralazine produced significant sinus tachycardia requiring IV propranolol in three patients, two of whom developed transient ST segment depression. These results indicate that labetalol is safe and effective for the control of postoperative hypertension, especially in those patients who are least able to tolerate tachycardia.

A homestyle delivery program in a university hospital.

The Homestyle Delivery Program, an alternative birth service at the University of California Davis Medical Center, Sacramento, is presented. The program was developed jointly by the departments of family practice, obstetrics, and pediatrics, in response to the needs and desires of patients and physicians to participate in a more natural family centered birthing process. A brief description of the program and data from the first 1 1/2 years of operation is given. This program, in contrast to many other alternative birthing programs, involves physicians in training; that is, residents in family practice and obstetrics who are being taught during their obstetrical training how to create and facilitate an intimate family oriented home-like birthing. Satisfaction with the program on the part of the participating families as well as physicians and program staff has been very high. Today, more families in this society are demanding this kind of alternative birthing experience; the Homestyle Delivery Program meets their needs and to data has demonstrated no increased risk to mother or infant.