Clinical features and outcomes of HIV-related cytomegalovirus pneumonia.

OBJECTIVE: To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia. DESIGN: Retrospective study. SETTING: A 900-bed acute facility in New York City. PATIENTS: Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-proven Pneumocystis carinii pneumonia (PCP) selected for comparisons by computer-generated random sequential numbers. MAIN OUTCOME MEASURES: Demographic, clinical, laboratory, radiological findings, and in-hospital mortality. RESULTS: Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l; P = 0.03) and presence of pleural effusions (33 versus 0%; P = 0.001) in CMV patients. Multivariate analysis showed that CD4 counts < or = 12 x 10(6)/l (odds ratio; 9.2; P = 0.029) and extrapulmonary CMV (odds ratio, 20.4; P = 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 +/- 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9; P = 0.002). The median time from admission to death was 31 days. CONCLUSIONS: CMV lung infection was seen in severely immunosuppressed HIV-positive patients and associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.

Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team.

OBJECTIVE: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. DESIGN AND METHODS: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. RESULTS: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. CONCLUSIONS: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.

Plasma propranolol before, during, and after cardiopulmonary bypass.

We evaluated changes in propranolol plasma levels before, during, and after cardiopulmonary bypass (CPB). Two groups of patients were studied, all of whom had been on long-term propranolol and had received their last oral dose 10 to 15 hr before surgery. Approximately 100 min before CPB began group 1 patients (n = 7) received 0.1 mg/kg propranolol intravenously while group II patients (n = 7) received a placebo. Before CPB the plasma propranolol levels fell in accordance with published descriptions for nonsurgical patients receiving oral and intravenous propranolol. Thereafter, the changes in the plasma levels were much the same in both groups. With the onset of CPB, the plasma levels decreased by approximately 50%. There was an insignificant fall in plasma levels during CPB, but the most interesting observation was made after : in each patient, the plasma levels obtained 5, 60, 120, and 240 min after CPB were higher than the last level during CPB. Mean plasma levels did not decline in either group during the 4-hr period. Although the reason for the sustained rise in the propranolol levels after CPB is not known, we suggest that it is due to the redistribution of propranolol from the lungs of the plasma coupled with reduction in hepatic elimination.

Surgical treatment of degenerative mitral regurgitation.

Between October 1965 and April 1975, mitral valve replacement was preformed in 66 patients with myxomatous degeneration of the mitral valve ("floppy valve syndrome"). Operative mortality was 6 percent (four patients). Current evaluation was obtained for all patients; the average postoperative follow-up interval for surviving patients was 3.5 years (range 1 month to 9.9 years); the total duration of postoperative follow-up for all patients was 180 patient-years. Overall survival rates, calculated by the actuarial method, were 81, 68 and 50 percent, respectively, 1, 2 and 5 years after mitral valve replacement. Preoperative variables with a significantly adverse effect on patient survival included patient age greater than 50 years, New York Heart Association functional class IV, left ventricular end-diastolic pressure greater than 12 mm Hg and mean pulmonary arterial wedge pressure greater than 16 mm Hg. Support is advanced for the concept that mitral valve dysfunction associated with myxomatous degeneration constitutes a broad spectrum of clinicopathologic involvement. Acute clinical and hemodynamic deterioration may often occur in the setting of chronic mitral valve dysfunction. Postoperative mortality is directly related to preoperative functional disability and hemodynamic evidence of impaired left ventricular function. Consideration should be given to earlier operative intervention in patients with myoxmatous mitral degeneration and mitral insufficiency before severe and probably irreversible impairment of ventricular function occurs.

Two dimensional Doppler echocardiographic/M mode echocardiographic and phonocardiographic method for study of extracardiac heterograft valved conduits in the right ventricular outflow tract position.

Significant concern exists over the long-term results of right ventricular outflow tract repair using heterograft valved conduits. Because these conduits and valves are difficult to image using ultrasound, a serially applicable two dimensional Doppler echocardiographic, M mode echocardiographic and phonocardiographic method for noninvasive investigation was developed and applied in 15 children. The method provides two dimensional echocardiographic imaging of valve contour and motion, as well as M mode and phonocardiographic analysis and quantitative range-gated Doppler information about the timing of flow through the conduit. Conduit diameter in two dimensional echocardiographic images correlated well with known conduit size (r = +0.96). A thickened and stenosed heterograft valve was predicted in two patients before hemodynamic investigation. This new method provides serially obtainable information to aid in the management of children and infants with a valved conduit placed for repair of congenital heart malformations and aids in planning the timing of hemodynamic follow-up studies.

Aspergillosis in the acquired immunodeficiency syndrome.

The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.

Effect of mitral regurgitation on the murmur of pulmonic regurgitation.

We evaluated auscultatory findings in a 67-year-old man with acquired pulmonic and mitral regurgitation. During inspiration, the murmur of pulmonic regurgitation decreased in intensity prior to surgery, but increased in intensity after mitral valve replacement. Inspiration reduces the volume of mitral regurgitation, thereby reducing the volume and murmur of pulmonic regurgitation.

Unusual complication of the Hancock porcine heterograft: strut compression in the aortic root.

A 65-year-old man underwent aortic valve replacement and triple coronary artery bypass grafting which were followed by gradual late postoperative thrombosis of his 25 mm. Hancock porcine aortic heterograft. At reoperation, the valve struts were noted to be angled centrally into the aortic lumen and dense thrombus completely filled all three sinuses. After valve removal and extensive debridement of the aortic anulus, including relaxing incisions, a diameter of only 23 mm. was obtained. A 23 mm. Björk-Shiley aortic prosthesis was inserted and the patient's recovery was uneventful. This previously unreported complication resulted from the insertion of a too-large Hancock porcine heterograft into a relatively small aortic root, resulting in circumferential strut compression, impedance of central flow, and subsequent valve thrombosis.

Early experience with minimally invasive direct coronary artery bypass grafting with the internal thoracic artery.

OBJECTIVE: Minimally invasive direct coronary artery bypass is performed under direct vision without sternotomy or cardiopulmonary bypass. The technique can be used in both primary and reoperative cases by employing the internal thoracic artery to perform arterial revascularization of the anterior surface of the heart. METHODS: Patients were selected who had significant coronary artery disease limited to 1 or 2 coronary distributions on the anterior surface of the heart. Coronary target vessels were grafted with the internal thoracic artery through a small anterior thoracotomy. After partial heparinization the anastomosis was facilitated by local coronary occlusion and handheld stabilization. RESULTS: Between August 1994 and July 1997, 162 patients underwent minimally invasive direct coronary artery bypass grafting with the internal thoracic artery. The left and right internal thoracic arteries were used for grafting of the left anterior descending artery in 142 patients (88%), the proximal right coronary artery in 7 patients (4%), existing saphenous vein grafts in 5 patients (3%), and diagonal branches in 2 patients (1%). Sequential grafting with the left internal thoracic artery was performed in 2 patients (1%) and bilateral internal thoracic artery grafting was performed in 4 patients (3%). Eight patients (4.9%) died within 30 days after the operation, 3 of cardiac causes. Seven additional patients died during the follow-up period. Nine patients (5.6%) required reintervention for graft stenosis or occlusion during follow-up. Of 141 patients seen 2 or more weeks after the operation, 135 (96%) had resolution of their anginal symptoms at a mean follow-up of 12 months (range 0-31 months). CONCLUSIONS: Anterior minimally invasive direct coronary artery bypass grafting with the internal thoracic artery avoids the risks of repeated sternotomy, aortic manipulation, and cardiopulmonary bypass. There was a low rate of reintervention, and patients had excellent resolution of anginal symptoms. Postoperative length of stay was comparatively short, and continued follow-up will be essential to evaluate long-term graft patency and patient survival.

Alterations in total and regional myocardial blood flow during acute rejection of orthotopic canine cardiac allografts.

Using radioactive microspheres, we studied the quantitative and sequential distribution of myocardial blood flow during acute rejection of cardiac orthotopic allografts in 15 nonimmunosuppressed dogs. During rejection mean cardiac output per kilogram decreased 49 percent from control, stroke volume per kilogram decreased 40 percent, total left ventricular flow decreased 43 percent, and the subendocardial/subepicardial flow ratio (I/O) of the left ventricular free wall decreased 21 percent. Relative subendocardial hypoperfusion occurred despite an increase in the ratio of left ventricle subendocardial supply (diastolic pressure-time index) to demand (tension-time index). The data indicate that total left ventricular flow decreases severely and selective left ventricular subendocardial ischemia develops very early during acute cardiac rejection.

Acute mitral valvular obstruction from infective endocarditis: echocardiographic diagnosis and report of the second successfully treated case.

Severe mitral stenosis of rapid onset and progression was observed in a patient with infective endocarditis superimposed upon mild rheumatic mitral valvular stenosis. This severe stenosis resulted from large vegetations impinging upon the mitral valve orifice. Preoperative studies indicating mitral stenosis with vegetations and pulmonary edema were followed by emergency mitral valve replacement, which was sucessful.

Increased regional myocardial perfusion after intracoronary papaverine in patients after coronary artery bypass grafting.

The objective of coronary artery bypass grafting (CABG) is to increase blood flow to ischemic areas of the myocardium. To determine if this was achieved, anterior wall myocardial perfusion was measured at rest and during intracoronary papaverine (5 mg), with the use of xenon-133 washout in 35 patients. Twelve control patients had no significant diameter narrowing (0% to 25%) of the left anterior descending coronary artery (LAD), 13 patients had greater than 50% narrowing of the LAD, and 10 patients had greater than 50% narrowing of the LAD with patent saphenous vein bypass grafts to the LAD. There was no significant difference in age. LVEDP, and global ejection fraction among the patients. There was no significant difference in anterior wall myocardial perfusion at rest between control subjects (61.0 +/- 3.7 ml/min/100 gm) and non-CABG LAD patients (60.2 +/- 5.4 ml/min/100 gm), or CABG LAD patients (63.4 +/- 4.8 ml/min/100 gm). After coronary arteriolar vasodilatation with papaverine, anterior wall perfusion increased in the CABG patients to 140.6 +/- 6.8 ml/min/100 gm. This was significantly greater (p less than 0.001) than the increase in the non-CABG LAD patients (72.8 +/- 8.1 ml/min/100 gm) but not different from the increase in the control subjects (145.3 +/- 8.4 ml/min/100 gm). In three cases, the same patients were studied before and after CABG with identical results. These data indicate that in patients with coronary disease, increases in myocardial perfusion are limited by the resistance of the proximal stenosis independent of vasodilatation distal to the stenosis. After successful CABG, the patent vein graft restores control of myocardial perfusion to the arteriolar bed.

Legionnaires' disease following cardiac transplantation.

The first two cases of Legionnaires' disease in heart transplant patients are reported. Of interest in these cases were culture of the organism from sputum, diagnosis by percutaneous lung aspiration, bronchopleural fistula formation in the first case, which was then successfully treated with multiple-tube thoracostomies, early cavitation of lesions in both cases after the start of antibiotic therapy, positive direct fluorescent antibody staining from transtracheal aspirate 42 days after starting appropriate antibiotic therapy in the first case, apparent superiority of intravenous erythromycin therapy in the first case, and survival of both patients. Our laboratory isolated and identified the organism in both cases.

Coronary artery bypass grafting in elderly patients. Comparative results in a consecutive series of 469 patients older than 75 years.

A consecutive series of 7104 patients undergoing isolated coronary artery bypass grafting during an 18-year period (1971 to 1988) included 469 patients older than 75 years. Results were analyzed to determine comparative risk factors for morbidity, early and late survival, and functional outcome. Patients younger than 75 years (group I) and patients older than 75 years (group II) were identical for ejection fraction and standard hemodynamic indices. Mean number of grafts and crossclamp time were greater for group II patients (p less than 0.01). Mean age of group I was 58.6 years and group II, 77.6 years (p less than 0.01). Women composed 19.7% (1308/6635) of group I and 36.2% (170/469) of group II patients (p less than 0.05). Mammary grafts were placed in 57.7% (3830/6635) of group I and 41.6% (195/469) of group II patients (p less than 0.05). Overall perioperative mortality rate was 2.1% for group I and 6.8% for group II (p less than 0.05). Perioperative myocardial infarction rate was similar for the two groups. Ventricular and supraventricular arrhythmias, renal insufficiency, neurologic complications, prolonged ventilatory support, increased hospital cost, and prolonged hospitalization were significantly more prevalent (all p less than 0.05) in patients older than 75 years. Five and 10 years postoperatively, there were no significant differences between groups I and II with regard to event-free status including angina, myocardial infarction, and reoperation. The 5-year survival rate was 92% for group I and 80% for group II (p less than 0.05), similar to that of age-matched control subjects. The significantly increased potential for complications and expense of coronary bypass in patients over 75 years of age mandates judicious patient selection and preoperative counseling. Despite a significantly increased early mortality and an anticipated decreased long-term survival paralleling normal life table survival curves, good intermediate functional improvement can be realized in patients older than 75 years, comparable with that expected in a much younger age group.

Diabetes mellitus and coronary artery bypass. Short-term risk and long-term prognosis.

A consecutive series of 3,707 patients over a 12 year period undergoing isolated coronary artery bypass grafting (CABG) included 250 diet/oral medication-controlled and 162 insulin-dependent patients with diabetes mellitus. Analysis of 20 pre- and 18 intra-operative variables revealed a higher incidence of hypertension, left ventricular hypertrophy, and tobacco consumption for both diabetic groups. The extent of diffuse coronary disease as judged angiographically and at operation was significantly greater in both diabetic groups than in nondiabetic CABG patients. No difference was noted in the incidence of localized coronary disease between the groups. Average number of grafts was greater in both diabetic groups. The perioperative mortality was greater for both diabetic groups (5.1% for non-insulin-dependent diabetes, 4.5% for insulin-dependent diabetes) than for nondiabetic CABG patients (2.5%). The incidences of sternotomy complications and renal insufficiency were equal in the diabetic groups and both were significantly greater than in the nondiabetic group. The number of total hospital days was also greater in both diabetic groups. Actuarially determined survival and cardiac event-free curves revealed no difference between the diabetic groups but a significant difference between both diabetic groups as compared to the nondiabetic patient population, with follow-up extending to 10 years after CABG. Results indicate that diabetic patients have quantitatively and qualitatively more coronary artery disease than nondiabetic patients and have higher perioperative morbidity and mortality and a lower long-term survival rate than nondiabetic patients. However, results continue to justify selection of patients for CABG based on clinical and anatomic criteria regardless of diabetic status. Diabetes mellitus should be considered a patient-related risk factor, both short- and long-term, following CABG.

Successful palliation using partial cardiopulmonary bypass in a two-day-old infant with type B interruption of the aortic arch.

Partial cardiopulmonary bypass from the pulmonary artery to the descending aorta was used successfully for resuscitation and aortic arch reconstruction in a 2-day-old infant with type B interrupted aortic arch. Partial cardiopulmonary bypass interrupted the fatal progression to acidosis and death caused by hypoperfusion of structures distal to the ductus arteriosus in this "ductus dependent" infant, and this approach provided time for an accurate dissection and anastomosis. The natural history, pathophysiology, and currently available surgical alternatives are considered in suggesting a possible role for partial bypass in the treatment interrupted aortic arch.

A rational approach to ligation of patent ductus arteriosus in the neonate.

During a 23-month period, 25 premature infants underwent ligation of a patent ductus arteriosus performed in the neonatal intensive care unit utilizing a limited posterolateral muscle-retracting incision. This approach afforded adequate exposure with minimal surgical time and trauma. All infants manifested severe respiratory distress and congestive heart failure. Both standard and contrast echocardiographic studies were used for noninvasive preoperative evaluation. Echocardiographic study proved to be a highly reliable and sensitive indicator of ductal patency. Eight infants (32 percent) died at 8 to 225 days of age. The primary cause of death was progressive pulmonary disease with subsequent failure of multiple organ systems. Seventeen (68 percent) of the 25 infants survived to leave the hospital. Advantages of ligation of a patent ductus arteriosus in the neonatal intensive care unit include the elimination of problems of transportation (thermoregulation, ventilation, and loss of lines) and continuity of ongoing care and monitoring. The standard facilities of the neonatal intensive care unit proved completely satisfactory for ligation of a patent ductus arteriosus. Ligation in the neonatal intensive care unit is suggested to minimize potential complications of care in the operating room and transport of these critically ill infants.

Reoperative coronary surgery. Comparative analysis of 6591 patients undergoing primary bypass and 508 patients undergoing reoperative coronary artery bypass.

During an 18-year period a consecutive series of 6591 patients underwent primary coronary bypass grafting and 508 patients underwent reoperative bypass. The mean patient age for the reoperative group was identical to that of the primary group, 59.8 years, but the mean age at initial operation for the reoperative group was 55.2 years. Mammary grafts were done at initial operation in 59% of patients who have had one operation versus only 46% of patients who subsequently required reoperation (p less than 0.001). The overall operative mortality rate was 2.0% (134/6591) for primary coronary bypass versus 6.9% (35/508) for reoperations (p less than 0.001). Patients with a reoperative interval of 1 to 10 years had a 6.0% (18/312) mortality rate, compared with 17.6% (13/74) for those in whom the interval between operations was greater than 10 years (p less than 0.01). Ventricular arrhythmias, excessive bleeding, prolonged ventilatory support, intraaortic balloon pump insertion (all p less than 0.05), and perioperative myocardial infarction (p less than 0.001) were all more prevalent after reoperations. Including perioperative mortality, the actuarial survival rate at 5 years was 80% for reoperations versus 90% for primary operations. The corresponding figures at 10 years were 65% and 75%. The probability of undergoing reoperation within 5 and 10 years was 0.034 +/- 0.003 and 0.055 +/- 0.005, respectively. Ten years postoperatively, 36% of patients having the initial operation had recurrent angina whereas 58% of the reoperative group had significant recurrent angina. Ten years after reoperation, 30% of operative survivors were free of heart-related morbidity and mortality compared with 50% of patients having a primary operation. Univariate analysis of factors increasing the probability of reoperation include the absence of a mammary graft and younger age at operation. Patients undergoing a second bypass operation represent a substantially higher risk subgroup than patients undergoing initial operation in terms of perioperative morbidity, mortality, decreased long-term survival, and decreased relief of recurrent cardiac morbidity.

Percutaneous transluminal coronary angioplasty. A growing surgical problem.

The incidence of prior percutaneous transluminal coronary angioplasty in surgical cases is nearly doubling yearly. In 1985, 11.4% of our bypass patients had one or more prior angioplasties. One hundred thirty-five patients with prior angioplasty are compared to 2,205 patients without angioplasty undergoing surgical revascularization. The mortality is 3.2 times higher in the angioplasty patients than in the control patients and the perioperative infarction rate is 2.5 times higher. Forty-four patients were taken directly to the operating room from the catheterization laboratory, 50 were operated on within 10 days, and 41 underwent operation more than 10 days after angioplasty. All of these late failures were of the lesion previously dilated. The infarction rate was less in patients taken immediately to the operating room on an emergency basis than in those whose operation was delayed up to 10 days (30% versus 70%). All patients who died had angioplasty of the anterior descending coronary artery. Angioplasty of this artery increases operative mortality should surgical treatment become necessary acutely. Patients should be informed before angioplasty of the increased surgical risks after a failed angioplasty procedure.

Diverse effects of stress and additional adrenocorticotropic hormone on digitalis-like compounds in normal and nude mice.

Digitalis-like compounds (DLC) are steroidal hormones that are synthesized in, and released from, the adrenal gland, whose regulation may be directed by the hypothalamic-pituitary-adrenal (HPA) axis. Increasing evidence points to antitumour properties of these compounds and we hypothesized that the establishment of tumours in athymic nude mice may be facilitated by an abnormal synthesis or secretion of DLC. To explore this hypothesis, DLC concentrations were determined in the plasma, and in adrenal and hypothalamic tissues of nude compared to normal mice under basal conditions, and 30 min after a stress stimulus (i.p. injection of 100 micro l saline) with or without additional adrenocorticotropic hormone (ACTH) 1 micro g/per animal. Simultaneously, plasma corticosterone and serum adrenocorticotropic hormone (ACTH) concentrations were analysed. The basal DLC concentrations were similar in the plasma and the hypothalamus of both strains, whereas the basal adrenal DLC concentration was significantly lower in the nude mice compared to normal mice. The stress stimulus induced in normal mice a significant increase in DLC concentrations in the adrenal gland, the plasma and the hypothalamus. However, in nude mice, it caused an increase only in the adrenal gland and the hypothalamus, whereas the plasma DLC concentration was not affected. In both strains, the administration of ACTH in addition to injection stress did not provoke a further increase in DLC concentrations while inducing a significant increase in plasma corticosterone concentration. Regardless of the applied stimulus, the nude mice expressed significant lower DLC concentrations in the adrenal gland and the plasma compared to normal mice. The low basal adrenal DLC concentration in nude mice and their impaired DLC response towards stress- and ACTH stimulation both support an involvement of DLC in tumorigenesis.