Central nervous system complications of coronary artery bypass graft surgery: prospective analysis of 421 patients.

A prospective analysis of 421 patients undergoing coronary artery bypass graft (CABG) surgery as the sole cardiac procedure was carried out to assess the frequency of central nervous system (CNS) complications. In all, 451 variables were assessed in each patient. Stroke occurred in 5.2% but was severe in only 2%. Prolonged encephalopathy occurred in 11.6% but usually resolved before discharge. No statistically significant pre- or intraoperative risk variables for CNS complications were found; specifically, age or pump times in excess of two hours were not significant factors. Postoperative use of an intraaortic balloon pump and pressor agents were significantly correlated with prolonged encephalopathy. The frequency of CNS injury in CABG surgery is similar to that in other forms of open heart surgery, and there has been little change in the frequency of CNS complications over the past seven years. Possible mechanisms of CNS damage during CABG surgery are discussed.

Therapeutic trial of cryofiltration in patients with rheumatoid arthritis.

Cryofiltration, a new technique for on-line plasma separation and its treatment by cold filtration, enables the selective removal of immune complexes and eliminates the need for replacement proteins. Fifteen patients with rheumatoid arthritis were treated for nine to 10 consecutive sessions over a three- to five-week period. Circulating immune complexes decreased by an average of 78 percent and rheumatoid factor by 32 percent. This was accompanied by significant clinical improvement in morning stiffness, articular index, 50-foot walking time, grip strength, and target joint circumference. Cryofiltration might thus be beneficial for a subgroup of rheumatoid arthritis patients in whom conventional therapy has failed.

Low-dose maintenance prednisone and antilymphoblast globulin for the treatment of acute rejection. A steroid-sparing approach to immunosuppressive therapy.

The purpose of this prospective randomized trial was to evaluate an immunosuppressive protocol involving reduced maintenance and antirejection steroid dosages in cadaver renal transplantation. The study comprises 23 first cadaver graft recipients who experienced an acute rejection episode. All patients received an initial 14-day course of antilymphocyte globulin (ALG) and azathioprine 1.5 to 2.0 mg/kg/day. In 11 patients (group 1), a low maintenance dose of prednisone (30 mg/day) was administered and first rejection episodes were treated with a second 10-day course of ALG. The remaining 12 patients (group 2) received high maintenance doses of prednisone (2 mg/kg/day with tapering) and intravenous methylprednisolone (IVMP) for first rejection episodes. Subsequent rejections in both groups were treated with high doses of steroids. In group 1, all first rejection episodes were reversed with ALG alone, 6 patients experienced no subsequent rejection, and 10 patients currently have a functioning graft. In Group 2, the first rejection episode was reversed with IMVP alone in 10 patients; in two patients in whom IVMP therapy was unsuccessful, ALG was then administered, and subsequent rejection reversal was effected. In group 2, 4 patients experienced no subsequent rejection, and 9 patients currently have a functioning graft. Patients in group 1 received significantly lower (P less than .01) cumulative steroid doses in the first six months following transplantation, which resulted in a reduced number of major infections, as compared with patients in group 2. We conclude that the steroid-sparing regimen of low maintenance prednisone and ALG for first rejection is as effective immunologically as the established high steroid protocol.

Breast reconstruction--selection, timing, and local recurrence.

Although reconstruction is now a standard part of the care of breast cancer patients, certain unresolved issues surround local recurrence. A percentage of women can be expected to develop local recurrence after mastectomy, whether or not they have reconstruction. This study provides a baseline for local recurrence in breast reconstruction candidates. Between 1955 and 1975, 1,110 patients underwent modified radical mastectomy at the Cleveland Clinic. This group of patients was analyzed to provide information about local recurrence in breast reconstruction candidates. The data were also analyzed for the effects of timing and nodal status. On the basis of this study, we have concluded that the number of involved axillary lymph nodes alone should not exclude a woman from having reconstruction. We also conclude that there is no oncological justification for imposing a specified waiting time between mastectomy and reconstruction.

A controlled randomized double-blind study of antilymphoblast globulin in cadaver renal transplantation.

Herein are presented the results of a controlled prospective randomized double-blind evaluation of antilymphoblast globulin as an immunosuppressive adjunct to azathioprine and prednisone in cadaver renal transplantation. There were 31 patients and 36 patients randomly assigned to therapeutic and control groups, respectively. ALG-treated patients experienced no major side-effects, a delayed onset of rejection following transplantation (P less than .005), a reduced total number of rejection episodes (P less than .05), fewer days in the hospital (P less than .05), a reduced cost of transplantation (P less than .02), improved graft survival (P less than .05), and patient survival equivalent to that of the control group. These data indicate that ALG is safe, cost-effective, and of immunologic benefit in cadaver renal transplantation.

Selective coronary arteriography: a clinical comparison of two contrast agents.

The radiopacity and complications of meglumine iothalamate 52% and sodium iothalamate 26% (Vascoray) were compared with those of meglumine diatrizoate 66% and sodium diatrizoate 10% (Renografin -76) in 2258 patients with and without cardiac disease. There was no difference in radiopacity and the type and incidence of adverse reactions were similar, but the frequency was significantly higher (p less than 0.05) with Vascoray in patients with constrictive pericarditis, dissecting aortic aneurysm, and primary pulmonary hypertension. The difference in the frequency of hypotension, sinus bradycardia, and transient asystole in the Renografin -76 and Vascoray groups was statistically significant. Ventricular arrhythmias occurred in 6% of the patients with primary myocardial disease compared to an average of 0.7% in those without this cardiac abnormality (p less than 0.01), but there was no significant difference in the frequency in the two contrast agent groups. All reactions were treated and the studies were performed without mortality. Results of this study show that iothalamate formulation with sodium to meglumine ratio of 1:2 containing 410 mEq/L of sodium (Vascoray) is suitable and safe for clinical use for roentgenographic studies of the heart, and coronary artery circulation.

Randomized controlled trial of transfer factor in Stage II malignant melanoma.

Thirty-six patients with Stage II malignant melanoma were randomized to no further therapy or transfer factor (TF) following surgical removal of all evident disease. Eighteen patients received TF, and 18 were in the surgery only group. Median disease-free intervals were 12.0 and 10.0 months, and survival, 40.8 and 27.0 months, respectively. Nine TF patients and four control patients remain alive. These differences were not statistically significant, and no adjuvant effect of TF could be demonstrated.

Sympathetic contribution to the cardiac response to stress in hypertension.

Studies of cardiac performance in hypertension have often been restricted to cardiac output determinations, although the latter alone are inadequate for that purpose. To define the range of cardiac performance in hypertension, the response of left ventricular filling pressure to increased workload (static exercise) was determined in 39 subjects--eight normotensive (NT) volunteers, seven patients with borderline hypertension (BLH), and 24 essential hypertensives (EH), of age-matched groups. A rise of mean pulmonary wedge pressure (PWP) by 5 mm Hg or more during maximum handgrip (HG) was considered "abnormal" for a workload (SBP x HR x 10(-3)) increase of greater than or equal to 25%. All NT subjects and all patients with BLH as well as 16 of the 24 EH (EH-I) showed normal cardiac performance by this definition. In contrast, PWP increased greater than or equal to 5 mm Hg during HG in eight patients with EH (EH-II). The calculated increase in cardiac workload was not significantly different among the four groups (+5, 5.8, 5.4 and 5.5 respectively). Beta blockade (propranolol, 10 mg i.v.) slowed heart rate in all subjects and reduced SBP x HR product in all groups both at rest and during HG. Responses of PWP to HG were widely divergent in the different patients. However, as a group those patients with "impaired cardiac performance" before propranolol (EH-II) had a greater reduction in performance following propranolol than EH-I or NT. This study suggests that adrenergic support of cardiac performance might be important in some hypertensive patients with no evidence of heart failure.

Failure of positive end-expiratory pressure to decrease postoperative bleeding after cardiac surgery.

To determine whether the application of positive end-expiratory pressure (PEEP) in the postoperative period after cardiac operation would reduce postoperative blood loss, the number of transfusions required, or the rate of reoperation for bleeding, we conducted a prospective study of 83 patients who underwent elective coronary revascularization. These patients were randomly assigned to receive either PEEP (10 cm H2O) or no PEEP (zero end-expiratory pressure). All other aspects of their care were identical. There was no statistically significant reduction in the amount of bleeding in patients treated with PEEP at 8 or 24 hours postoperatively. There was no significant difference in hematocrit between the groups preoperatively or postoperatively. There was no statistically significant difference in the number of reexplorations for bleeding. Finally, there was no significant difference between the groups in the amount of blood administered. On the basis of our results, we conclude that the application of PEEP in the postoperative period of cardiac operation did not reduce the amount of blood loss, the need for reexploration for bleeding, or the blood requirements in this group of patients.

Long-term results of renal transplantation in recipients with a functioning graft for 2 years.

The late results of renal transplantation are reviewed in 214 recipients with a functioning allograft for 2 years. Graft survival was better (P less than 0.001) in living related recipients (t 1/2 = 17 years) compared with cadaver graft recipients (t 1/2 = 7.7 years). Graft survival was also significantly different (P less than 0.001) in patients with a 2-year serum creatinine level of less than or equal to 2.0 (t 1/2 = 16.4 years), 2.1 to 3.0 (t 1/2 = 6.5 years), or greater than 3.0 mg/dl (t 1/2 = 2.9 years). A greater proportion of patients with a 2-year serum creatinine level of greater than 3 mg/dl had experienced greater than two rejection episodes (P less than 0.0001). Among recipients with a 2-year serum creatinine level of less than or equal to 2.0 mg/dl, living related grafts achieved better graft survival than cadaver grafts (P less than 0.05). Major complications of transplantation were more common in patients with a cadaver graft, 2-year serum creatinine level of greater than 3 mg/dl, or age greater than 45 years. One hundred and forty-two patients are currently alive, 93% of whom have achieved complete rehabilitation.

Peripheral nervous system complications of coronary artery bypass graft surgery.

Among 421 patients undergoing coronary artery bypass graft surgery, 55 (13%) developed 63 new peripheral nervous system (PNS) complications postoperatively. Most common was a brachial radiculoplexopathy, which occurred in 23 patients. Of these, 21 involved lower trunk or medial cord fibers. In 17 there was a correlation between the site of jugular vein cannulation and the side affected, suggesting that needle trauma played a role. Stretching from chest wall retraction may have caused some cases. Other deficits included 13 saphenous, 8 common peroneal, and 5 ulnar mononeuropathies. Six patients had persistent singultus, suggesting phrenic nerve involvement. Unilateral vocal cord paralysis was found in 5. An isolated partial Horner syndrome and a facial neuropathy were also identified. Males were more likely to develop PNS complications. Hypothermia during surgery was associated with increased risk. Most PNS deficits were transient, and lasting disability was rare.

Pruritus of cholestasis treated with plasma perfusion.

Patients with uncontrollable pruritus secondary to cholestatic liver disease were subjected to plasma perfusion in an attempt to remove the toxins responsible for this symptom. The improvement in the degree of pruritus was dramatic and surprisingly long-lasting in five of six patients. One patient had a response more difficult to evaluate. Serum bile acids levels fell in all patients in whom pruritus improved but not in the patient who responded less favorably.

Influence of estrogen receptor status on response to combination chemotherapy for recurrent breast cancer.

To determine the influence of cytoplasmic estrogen receptor (ER) status on response to chemotherapy among patients with recurrent breast cancer amenable to biopsy, we studied 65 patients who had ER determinations performed on metastatic lesions. The response to combination chemotherapy and duration of survival were determined in 49 of these patients who receive cytotoxic chemotherapy as their sole modality of treatment. Compared to patients with ER levels less than 3 femtomols/mg, patients with an ER concentration greater than or equal to femtomols/mg had a higher response rate (57% vs 21%, P less than 0.05) and a longer survival (35 vs 13 patients was attributable to response to subsequent hormonal manipulations. These differences between ER-positive and ER-negative patients were lessened by redefining ER-positive as greater than 10 femotomols/mg. Nevertheless, at our institution patients with ER-positive metastatic breast cancer have a higher response rate to chemotherapy and survive longer than their ER-negative counterparts.

Reactions to contrast media: testing the CNS hypothesis.

Sodium iothalamate was injected intravenously into mice to test the hypothesis that reactions to contrast media are controlled by the central nervous system. Particular emphasis was placed on (a) the effect of the limbic portion of the brain on the hypothalamus and (b) the outflow through the autonomic nervous system. Diazepam and hexamethonium significantly affected the LD50; in addition, in comparison trials with control mice, they markedly decreased the death rate (p < 0.0005). High doses of methylprednisolone sodium succinate, given every 6 hours before the contrast medium, had no effect.

HDL-cholesterol concentration and severity of coronary atherosclerosis determined by cine-angiography.

We studied 226 adult male subjects (mean=52yr) who underwent coronary arteriography. Their serum lipid and lipoprotein levels [total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-C, HDL-phospholipid (HDL-P), HDL-TG, HDL-C/TC, HDL-P/TC, LDL-C/TC, LDL-C/HDL-C and LDL-C/HDL-P] were correlated with the severity of coronary artery disease (CAD). Studies showed a slight but statistically significant correlation (linear regression) between CAD and HDL-P/TC (r=-0.24, P < 0.001), HDL-C/TC (r=-0.20, P < 0.002), followed by LDL-C/HDL-P (r=0.19, P < 0.004) and HDL-P (r=-0.18, P < 0.008). HDL-C, LDL-C and TC were significant at the P < 0.05 level; P value of TG was non-significant. Subjects were conveniently grouped based on degree of coronary artery narrowing: normal, mild (1-50%); moderate-severe (51-99%) and very severe (100% occlusion). Of the 11 lipid variables, the best predictor of the stage of the CAD was HDL-P/TC as measured by one-way analysis of variance. This trend was unaltered even after adjustment for covariates. HDL-P, LDL-C/HDL-P and HDL-C/TC were also significant, but the other lipid parameters were not. The study indicates that HDL-C, by itself, is not as effective a predictor of CAD as HDL-P/TC. Also, the small but statistically significant inverse relationship between HDL-P/TC and CAD suggests that a low HDL-P/TC ratio can be considered a risk factor for CAD but not as a dependable clinical diagnostic aid for predicting the severity of CAD on an individual basis.

Prognostic factors affecting remission, remission duration, and survival in adult acute nonlymphocytic leukemia.

The medical records of 94 consecutive patients with acute nonlymphocytic leukemia (ANLL) were reviewed to identify significant prognostic factors. The data were analyzed using 1) Cox's linear hazard and linear logistic models, 2) chi-square comparison of the groups living longer than 2 years and those living less than 2 years, and 3) the Gehan-Breslow test of equal survival curves. The only statistically significant finding was that the presence of promyelocytic cell type and complete remission correlated with increased survival (p less than .05), but this was negated by the small number of patients with this cell type. There was a suggestive association between higher initial hemoglobin and survival (p = .09). The Gehan-Breslow test revealed a possible difference in survival between those patients more than 51 years of age and those less than 51 (p = .10). Thus none of the commonly accepted prognostic factors in acute nonlymphocytic leukemia was definitely shown to be useful. The findings of this study support an aggressive approach toward all patients with this disease.