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Biomedical subjects

J A Mannick

Publications and source records attributed to J A Mannick.

At least 145 records · Page 8Linked to original sources
PubMed1984

Early carotid endarterectomy in patients with small, fixed neurologic deficits.

Patients who have sustained a large hemispheric stroke are not candidates for early carotid endarterectomy, but there is less agreement regarding the role of carotid endarterectomy in patients with small, fixed neurologic deficits. Accepted practice in many centers is to wait 4 to 6 weeks after the onset of the deficit before proceeding with carotid endarterectomy because of the fear that early revascularization will increase the size of the infarct. Earlier endarterectomy, however, in patients with significant residual ipsilateral carotid territory at risk may prevent repeated infarctions. For the past 5 years our approach to patients with a small stable stroke and significant stenosis (greater than 75%) has been prompt ipsilateral endarterectomy. Of the 337 carotid endarterectomies at our institution since 1979, a subset of 28 patients with hemodynamically significant carotid lesions presented with a small, fixed stroke. The period of time between the appearance of the stroke and carotid endarterectomy averaged 11 days, but 53% of patients were operated on within 7 days of the onset of symptoms. Selective shunting based on intraoperative EEG monitoring was utilized and 40% of the 28 patients required shunts. Operative mortality consisted of one death from a pulmonary embolus, and no patient sustained a new postoperative deficit. Long-term follow-up was available for 96% of patients over a mean of 2 years. During this time two new neurologic events occurred: one fatal stroke and one transient deficit. This experience indicates that patients with small, fixed neurologic deficits who continue to have carotid territory at risk may safely undergo carotid endarterectomy without waiting 4 to 6 weeks.

Aged↗
PubMed1983

The place of abdominal aortography in abdominal aortic aneurysm resection.

We analyzed 110 patients who underwent abdominal aortography as a routine preliminary to abdominal aortic aneurysm resection. In 11 of the 15 patients for whom the procedures were useful in planning the operative tactics, the aortograms would have been performed anyway on clinical indications. In two patients, the changes in surgical maneuvers would not have been made through anatomic inspection at the time of the operations, but the lesions were asymptomatic. Biplane views and views of the femoropopliteal systems were rarely influential. Morbidity from the angiography was minimal and mortality was zero, but about seven aortograms were performed for each one that effected a change in procedure. We concluded that abdominal aortography as a preliminary to aneurysmectomy could be reasonably limited to patients in whom it was indicated by clinical features, including important hypertension, impaired renal function, diminished or absent femoral pulses, suspected mesenteric ischemia, suspected suprarenal extension of the aneurysm, or suspected (from the chest roentgenograms) thoracic aneurysm.

Aorta, Abdominal↗
PubMed1983

Coexistent carotid and coronary artery disease. Surgical management.

We performed simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CE) in 42 patients (average age, 61 years). Twenty-nine patients had preoperative transient ischemic attacks. Carotid arteriography showed stenosis (greater than 70%) in 38 subjects and extensive ulcerated lesions in two, and two emergency patients were not studied. Carotid artery dissection and sternotomy were simultaneously performed and the patients were cannulated for cardiopulmonary bypass (CPB). We undertook CE (22 left and 24 right) using EEG monitoring prior to CPB in all but one patient. The average carotid occlusion time was 25 minutes without a shunt in 23 patients and 5.5 minutes with a shunt in 19 patients. After CE, CABG was performed with an average aortic clamp time of 39 minutes and an average CPB time of 87 minutes. The operative mortality was 5% (2/42). There were no strokes or perioperative myocardial infarctions. Neurologic morbidity consisted of postoperative headache in one patient, transient upper-extremity weakness in two patients, and transient facial weakness in one patient. The average length of postoperative hospitalization was ten days. Currently, patients with symptomatic coronary artery disease and concomitant carotid bruits with positive noninvasive testing and arteriography should have simultaneous repair of these lesions.

Aged↗
PubMed1983

Fatal infection in mice after injection of immunosuppressive serum fractions from surgical patients.

Following surgical or accidental trauma many patients show suppression of cellular immunity. In this investigation sera from severely burned patients and patients undergoing aortic aneurysm repair were studied. Sera shown to suppress phytohaemagglutinin-induced blastogenesis of normal human lymphocytes were fractionated using ion exchange and G25 Sephadex chromatography. Suppressive activity was largely confined to a low molecular weight (LMW) fraction and was dose dependent. LMW fractions of normal sera had no significant suppressive activity. The purpose of this study was to test the causal relationship between immunosuppressive serum and decreased resistance to bacterial infection. Listeria monocytogenes infected mice were used as an in vivo model to test suppression of cellular immunity. Injection of LMW fractions of suppressive sera significantly increased mortality in these mice, but had no effect on non-infected mice. There was good correlation between the in vitro and in vivo effects of the suppressive fractions. These results suggest that a circulating factor in the serum of injured patients suppresses cellular immunity and may be responsible for impaired resistance to infection.

Adult↗
PubMed1983

Inhibition of the production of a soluble helper mediator by cyclosporin A results in the failure to generate alloreactive cytolytic cells in mixed-lymphocyte culture.

The mechanism of action of cyclosporin A (CsA) in inhibiting the induction of alloreactive cytolytic T lymphocytes (CTL) in mixed-lymphocyte culture (MLC) was investigated. CsA at concentrations of 10(-3) to 10(-1) micrograms/ml completely prevented the generation of CTL. However, the addition of culture supernatants from mitogen-activated lymphocytes to MLC not only significantly reversed the suppressive effect of CsA but also fully restored the reactivity of lymphocytes already treated with CsA. By measuring the presence of a soluble helper mediator (SHF) in MLC supernatants, we found that CsA-treated lymphocytes produced no SHF, possibly interleukin 2 (IL-2). The effect of CsA on receptors for IL-2 was subsequently studied and it was found that the binding capacity of 125I-labeled IL-2 to lymphocytes was not altered by the presence of CsA. These findings suggest that the prevention of helper cells from producing SHF, rather than the inhibition of the response of effector cells to SHF, is a possible explanation for the immunosuppression mediated by CsA.

Animals↗
PubMed1983

Lymphocyte function in the critically ill surgical patient.

Lymphocyte function is commonly altered in critical ill surgical patients. There is controversy whether or not formation of antibodies is impaired; however, cellular immune responses are routinely depressed. Patients who have suffered major surgical or accidental trauma or burns frequently become anergic. Their lymphocytes respond poorly to mitogenic or antigenic stimulation, and serum factors suppressive of lymphocyte activation appear. Mechanisms underlying these abnormalities remain to be defined.

Anesthesia↗
PubMed1983

Routine electroencephalographic (EEG) monitoring during carotid endarterectomy.

Controversy continues concerning the advisability of routine shunting, no shunting, or selective shunting during carotid endarterectomy. Because of its reflection of the physiologic state of the end organ, the authors chose routine 18 lead EEG monitoring as a guide to selective shunting and as an indication of adequate shunt function during all carotid endarterectomies performed from December 1977 through July 1982. In that period, 200 patients underwent 219 endarterectomies under general anesthesia and EEG monitoring. Ischemic EEG changes at the time of carotid cross clamping suggested the need for intraluminal shunts in 16% of patients. Insertion of shunts restored the EEG pattern to normal in all instances, although in two patients, adjustment of the shunt was required to maintain this results. EEG changes requiring shunting occurred in 10% of patients with unilateral disease, in 27% of patients with bilateral disease, and in 42% of patients with unilateral stenosis and contralateral occlusion. Twenty-seven patients had small fixed neurologic deficits before operation. Surgery was not delayed in these individuals who demonstrated no increased requirement for shunts and no new postoperative neurologic deficits. In the group of 150 endarterectomies performed as separate procedures, there was one (0.7%) fixed neurologic deficit after operation, one transient deficit (0.7%), and one death (0.7%). Sixty-nine endarterectomies were performed simultaneously with open heart surgery and were associated with one fixed neurologic deficit (1.4%) and two transient deficits (2.9%). All four deaths in this group were attributable to the cardiac surgical procedures. These results indicate that selective shunting based on EEG monitoring permits the safe performance of carotid endarterectomy, even in patients considered to be at high risk for postoperative neurologic deficit.

Adult↗
PubMed1982

Anergy, immunosuppressive serum, and impaired lymphocyte blastogenesis in burn patients.

Skin testing with four recall antigens was performed serially in 21 patients after a major thermal burn. We looked for a correlation between the occurrence of anergy, the presence of immunosuppressive serum, and the impairment of the lymphocyte-proliferative response to phytohemagglutinin (PHA). Serum cortisol, endotoxin, and prostaglandin E2 (PGE2) levels were also measured in the serum or plasma. When anergy developed, it became apparent early in the course of the illness. It did not correlate closely with the severity of the burn, but was associated with mortality. There was a good correlation between anergy and coexisting serum suppression of lymphocyte activation in vitro. This serum immunosuppressive activity was not related to serum cortisol, PGE2, or plasma endotoxin levels. Anergy also correlated with coexistent impairment of patient peripheral blood lymphocyte activation by PHA. These results suggest that both immunosuppressive serum and an impaired lymphocyte response to mitogens are associated with anergy in burn patients and confirm that the development of anergy is an index of poor prognosis.

Adult↗
PubMed1982

Depressed immune response in burn patients: use of monoclonal antibodies and functional assays to define the role of suppressor cells.

Recent experimental evidence has suggested that circulating suppressor leukocytes play an important role in mediating the suppression of immunity seen in burn patients. In order to shed further light on the relationship between suppressor cells and depressed cellular immunity 22 patients were studied (mean age 37) who had suffered severe burns of greater than 30% body surface area. Simultaneous studies were performed on 14 control laboratory personnel (mean age 32). Monoclonal antibodies were used to identify T-lymphocyte subsets known to have suppressor/cytotoxic (OKT8) and helper/inducer (OKT4) function, respectively. In addition, serial measurements were made of the response of circulating lymphocytes to the T-cell mitogen phytohemagglutinin (PHA). An inversion of the normal ratio between suppressor/cytotoxic and helper/inducer subsets (normal 0.55:1, postburn 1.4:1; p less than 0.001) occurred soon after burn injury, reached a peak in five to seven days and then returned gradually to normal levels by 14 days. A diminished response of patients' lymphocytes to PHA (57 +/- 10% SD suppression as compared with normal controls at five to seven days) corresponded with high suppressor to helper cell ratios and returned to normal at the same time. Functional assays, which recognize only high levels of activity, demonstrated circulating suppressor cells in nine patients during this same period but became negative by 14 days. These early immunologic modulations were not predictive of morbidity or mortality. Later in the postburn course, systemic sepsis in eight patients was associated with a return of increased suppressor to helper cell ratios and decreased mitogen (PHA) responsiveness. At this time functional assays demonstrated circulating suppressor cells in six patients. Five of these six patients died of sepsis. It was concluded that severe burn injury regularly induces an early transient increase in circulating suppressor cells accompanied by a depression of lymphocyte activation. A later (greater than 14 days postburn) increase in suppressor cells to levels detectable by functional assays is closely correlated with mortality from sepsis.

Adult↗
PubMed1982

Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin A.

Mice sensitized with alloantigens and treated with cyclosporin A (CsA) were incapable of generating antigen-specific cytolytic lymphocytes (CL). Lymphocytes from these CsA-treated animals could not be reactivated upon exposure to the same alloantigens in mixed lymphocyte culture (MLC), whereas their response to a third-party antigen remained intact, suggesting a long-lasting and specific effect of CsA. After being irradiated, these lymphocytes from CsA-treated animals were added to normal MLC and were shown to prevent normal lymphocytes from becoming cytolytic in a dose-dependent and antigen-nonspecific fashion. These suppressor cells were not detected in mice receiving CsA only, indicating that CsA did not induce but rather permitted the expression of suppressor cells possibly generated by allosensitization. The suppressor cells appeared to be T lymphocytes, because treatment with anti-Thy-1.2 antibody and C abrogated their suppressive activity. The present results suggest that activation and/or sparing of suppressor cells by CsA may account for the long-lasting unresponsiveness seen in CsA-treated animals.

Animals↗
PubMed1982

Association of impaired immune responsiveness of lymphocytes from animals bearing large tumors with a membrane-bound suppressive substance.

The immunoreactivity of lymphocytes from mice bearing large tumors was investigated. As compared to normal lymphocytes, lymphocytes from tumor bearers manifested a lessened proliferative response to T-cell mitogens and were less capable of destroying syngeneic tumor target cells. However, the impaired reactivity of these lymphocytes was improved significantly after washing repeatedly in tissue culture medium in vitro. The increase in cytolytic activity was tumor specific. A membrane-associated suppressive substance was detected in the washing medium which inhibited the cytotoxicity of washed lymphocytes. The effect of suppressive substance was tumor specific and sensitive to treatment with protein A and anti-immunoglobulin antibody, indicating that the suppressive substance contained immunoglobulin. The present findings suggest that a membrane-associated suppressive substance(s) may be in part responsible for the diminished immune responsiveness of lymphocytes from animals bearing large tumors.

Animals↗
PubMed1982

The fate of bypass grafts to an isolated popliteal artery segment.

From 1967 to 1982, 55 patients underwent 64 femoropopliteal bypass grafts into an isolated popliteal artery segment. Seventy-six percent of these patients had threatened limb loss from advanced atherosclerosis, and 24% had disabling claudication. Forty-five percent of the patients were diabetic. The 30-day operative mortality rate was 1.6%, and the 30-day postoperative amputation rate was 3.2%. Graft potencies were analyzed by the life table method. The 2-year graft patency rate was 70.6%, and the 5-year patency was 60.7%. The 2- and 5-year limb salvage rates were each 83%. With evidence for decreased graft function, four grafts (6%) were successfully revised before failure occurred. Among 10 polytetrafluoroethylene grafts followed up to a maximum of 48 months, there was one early postoperative occlusion, one long-term occlusion, and one early amputation. With respect to patency and limb salvage, the results of isolated popliteal artery segment grafts fall between the 5-year patency and limb salvage rates for autogenous vein grafts to popliteal arteries with at least one tibial vessel runoff (78% patency and 89% limb salvage) and the rates for femoral-tibial/peroneal grafts (5-year patency 56%, limb salvage 69%). An isolated segment is an appropriate recipient vessel for a reconstruction for limb salvage, and reasonably good results can be anticipated.

Actuarial Analysis↗
PubMed1981

Results of xenogeneic I-RNA therapy in patients with metastatic renal cell carcinoma.

Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.

Animals↗
PubMed1981

Intraoperative arteriography in femoropopliteal and femorotibial bypass grafts.

We reviewed our experience with intraoperative arteriography following femoropopliteal and femorotibial reconstruction during a five-year period beginning in January 1975. During 171 of 250 procedures an intraoperative arteriogram was performed. In nine (5.2%) instances, a correctable abnormality was detected. These consisted of three cases of distal anastomotic stenoses, two cases of intimal flaps, three cases of poor inflow, and one case of clot. Intraoperative arteriography may reveal a correctable abnormality in 5% of femoropopliteal and femorotibial bypass grafts and thus prevent early graft failure. The false-positive rate was 0.06%. In our experience, routine intraoperative arteriography has been a safe, easy to perform, and effective method of assessing technical problems in femoropopliteal and femorotibial reconstruction.

Femoral Artery↗