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J A Mannick

Publications and source records attributed to J A Mannick.

At least 73 records · Page 4Linked to original sources
PubMed1993

Molecular mechanisms of decreased interleukin-2 production after thermal injury.

BACKGROUND: Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury. METHODS: Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies. For measurement of IL-2 production, cells were cultured with either concanavalin A or a combination of the phorbol ester PMA, which directly activates protein kinase C, and the calcium ionophore A23187, which increases intracellular calcium. Cytokine mRNA expression was measured by Northern blot analysis and IL-2 production by bioassay. RESULTS: Both IL-2 production and IL-2 mRNA expression were consistently suppressed in concanavalin A-stimulated cells from burned mice compared with sham burns. This suppression of IL-2 and IL-2 mRNA also occurred when T cells were activated with PMA and A23187, bypassing the earlier stages of the signal transduction mechanism. IL-1 beta and tumor necrosis factor-alpha mRNA expression were consistently increased in burned animals, indicating that decreased IL-2 mRNA expression was specific to IL-2 and not representative of a global decrease in cytokine mRNA expression. CONCLUSIONS: These results suggest that the principal cellular abnormalities that result in altered T cell activation and IL-2 production after thermal injury lie downstream of the initiating signal transduction events and before IL-2 gene transcription.

Animals↗
PubMed1993

Risks and benefits of femoropopliteal percutaneous balloon angioplasty.

PURPOSE: The purpose of this study was to evaluate the efficacy of angioplasty in the treatment of femoropopliteal arterial disease. METHODS: From 1980 to 1991, 126 angioplasty procedures were performed in 131 limbs of 106 patients with 175 femoropopliteal lesions (26 common femoral, 118 superficial femoral, and 31 popliteal). Critical ischemia was present in 55 limbs (42%), and claudication was present in 76 (58%). Angioplasty was performed for a single lesion in 87 limbs (66%) and for multiple lesions in 44 (34%). In 13 limbs (10%) the most severe lesion was an occlusion; in 118 (90%) all lesions were stenoses. Distal runoff was good (2 or 3 vessels patent) in 72 limbs (55%) and poor (0 or 1 vessel patent) in 59 (45%). RESULTS: Death within 30 days occurred in 0.8%, nonfatal systemic morbidity in 7.1%, and local morbidity in 1.6% of procedures. Multivariate analysis revealed that indication and age were predictive of increased morbidity and mortality rates. Immediate success was achieved in 95% of limbs treated. Mean follow-up time was 2.0 years. The overall 5-year cumulative primary patency rate was 45% (+/- 5%). In a proportional hazards model indication and lesion type were predictive (p < 0.01) of long-term failure, with relative risks of 2.0 (1.2 to 3.3) and 2.7 (1.3 to 5.6), respectively. The 5-year primary patency rate after angioplasty for stenoses and claudication was 55% (+/- 7%), for stenoses and critical ischemia it was 29% (+/- 11%), and for occlusions it was 36% (+/- 14%). CONCLUSION: These results suggest that femoropopliteal angioplasty is a low-risk procedure with acceptable long-term results in patients with claudication and stenoses.

Angioplasty, Balloon↗
PubMed1992

Modulation of macrophage hyperactivity improves survival in a burn-sepsis model.

Macrophage hyperactivity with increased production of tumor necrosis factor, interleukin 6, interleukin 1, and prostaglandins has been demonstrated in the injured patient, but the effect of this on the clinical outcome is unclear. We studied the effect of combination interleukin 1 beta and indomethacin sodium therapy on macrophage hyperactivity and survival after sepsis in a murine burn model. Macrophage interleukin 1, interleukin 6, and tumor necrosis factor alpha production were all significantly increased 10 days after thermal injury. Treatment with recombinant human interleukin 1 beta in combination with indomethacin significantly reduced this overproduction of cytokines to normal levels, and this was associated with an improvement in survival after septic challenge (52% survival in interleukin 1 beta-indomethacin-treated group compared with 22% in burned vehicle control mice). Burned mice that received either interleukin 1 beta or indomethacin alone demonstrated tumor necrosis factor and interleukin 6 production and survival intermediate between the interleukin 1 beta-indomethacin-treated group and the vehicle control group. Control of macrophage hyperactivity is associated with improved survival from subsequent sepsis and offers a potential new strategy for the treatment of immune dysfunction in thermally injured patients.

Animals↗
PubMed1992

Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2.

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.

Abdomen↗
PubMed1992

Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath.

The timing of carotid endarterectomy (CEA) and coronary revascularization (CABG) for concomitant disease is controversial. Results of combined CEA/CABG in 127 patients (age range, 46 to 82 years; mean age, 65 years; 61% male) from 1978 to 1991 were reviewed. Ninety-five patients (75%) were in New York Heart Association functional class III or IV, 48 (38%) had left main coronary artery disease, and 32 (28%) had depressed ejection fraction ( < 0.50). Forty (32%) had asymptomatic bruits, 61 (48%) transient ischemic attacks, and 26 (20%) prior strokes. Seventy-five (59%) had bilateral carotid stenosis, including 20 (16%) with contralateral occlusions. Perioperative mortality was 7 of 127 (5.5%), and all deaths were cardiac related. Myocardial infarctions occurred in 6 of 127 patients (4.7%) and were nonfatal in 3 (2.3%). Permanent strokes occurred in 7 of 127 (5.5%) and were ipsilateral in 5 (3.9%). Perioperative stroke did not occur in the asymptomatic group, but the risk was higher in those with prior stroke (19%) or with contralateral carotid occlusion (15%). The stroke risk for our patients with carotid disease having CABG without CEA is not known, but the literature reports rates as high as 14%. For our patients without known concomitant disease, the risk of permanent stroke was 1.0% (31/3012) for isolated CABG and 1.5% (7/482) for isolated CEA. The late results after CEA/CABG revealed a 5-year survival of 70% +/- 5%, which correlated with ejection fraction ( > or = 0.50, 81% +/- 5%; < 0.50, 45% +/- 11%; p < 0.003). Freedom from late permanent ipsilateral stroke was 97% +/- 2% at 8 years. Freedom from stroke at 5 years was lower among patients with a previous stroke (71% +/- 10%) compared with transiently symptomatic (90% +/- 4%) and asymptomatic (96% +/- 4%) patients (p < 0.03). Combined CEA/CABG is a useful option in this high-risk group of patients with extensive atherosclerosis; avoids a subsequent hospitalization, anesthetic, and delay period; and provides long-term protection from ipsilateral stroke.

Actuarial Analysis↗
PubMed1992

Prospective double-blinded comparison of MR imaging and aortography in the preoperative evaluation of abdominal aortic aneurysms.

The authors conducted a prospective double-blind study comparing spin-echo axial and coronal magnetic resonance (MR) imaging with aortography in the preoperative evaluation of 20 patients with abdominal aortic aneurysms. Receiver-operating-characteristic (ROC) analysis was used to evaluate the performance of MR imaging versus aortography in assessing arterial stenotic disease. Both modalities were equivalent in demonstrating the upper extent of the abdominal aortic aneurysms with respect to the renal and visceral arteries. MR imaging was superior in demonstrating aneurysmal iliac arteries and intraluminal thrombus. Although aberrant venous anatomy, associated pathologic changes, and other concomitant lesions were demonstrated with MR imaging, it performed poorly in assessing arterial stenoses and occlusions. Thus, the authors caution against the routine substitution of spin-echo MR imaging for aortography in the evaluation of abdominal aortic aneurysms. Conventional angiography should continue to be performed in patients with suspected mesenteric ischemia, significant hypertension, and symptomatic iliofemoral atherosclerosis, at least until robust MR angiographic techniques have proved themselves under similar rigorous clinical evaluation.

Aged↗
PubMed1992

Causes of primary graft failure after in situ saphenous vein bypass grafting.

In situ saphenous vein bypass grafts originating in the groin were performed in 455 consecutive patients. Primary failure occurred in 92 grafts during follow-up, including 22 (4.8%) with nonocclusive stenosis and 70 (15.4%) with occlusion. The cause for failure could not be determined in seven grafts; 104 contributory causes were identified in the remaining 85 grafts. Among the 104 likely causes, 66 (63%) were intrinsic to the graft itself and contributed to failure of 55 (12.1%) of 455 grafts. These causes included perianastomotic stenosis (48), vein stricture (14), focal vein stenosis (10), valvulotome injury (9), kink (6), retained valve leaflet (4), intimal flap (3), and residual arteriovenous fistula (2). Among these intrinsic causes, 20 were directly related to the in situ technique, contributing to failure of 15 (3.3%) of 455 grafts. Thirty-eight (37%) of the 104 causes were extrinsic to the graft, including compromised inflow (2) or outflow (19), hypercoagulability (9), systemic hypotension (6), and graft sepsis (2). Hypothetically, improvements in technique, patient selection, and perioperative management might have eliminated 46 (44%) of 104 causes of primary graft failure. Delayed graft and anastomotic stenosis and late progression of outflow disease remain resistant to modern therapy.

Aged↗
PubMed1992

Suppressor T-cell levels are unreliable indicators of the impaired immune response following thermal injury.

The presence of increased levels of suppressor T cells after thermal injury and their relevance remain controversial. It is unclear whether suppressor T cells are the cause or result of sepsis complicating thermal injury. Spleen cells from a standardized murine burn model and sham burn controls were studied and the relationship between the levels of suppressor cytotoxic T cells (CD8, Lyt-2+), helper T cells (CD4, L3T4+), response to concanavalin A (ConA) and to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production was examined. Mortality following infection via cecal ligation and puncture (CLP) of matched controls was also studied. At day 7 postburn, mean ConA (70 +/- 12% of control) and PHA response (58% +/- 5.2% of controls) and IL-2 production (43% +/- 5.4%) were significantly less than sham burn values (100%; p less than 0.05). However, the mean percentage of cells staining with anti-Lyt-2 and anti-L3T4 (9.1 +/- 0.59 and 13.9 +/- 0.65) was similar to the mean percentage in sham burn animals (9.4 +/- 0.65 and 16.6 +/- 1.1). Furthermore, no significant differences were observed between burned mice and controls in helper (17.3% +/- 1.8% burn vs. 21.2% +/- 1.7% sham) or suppressor cell levels (7.8% +/- 1.2% burn vs. 8.6% +/- 0.7% sham) or helper-suppressor ratios on day 10 postburn. Mortality of 20 litter-matched controls subjected to CLP on day 10 postburn was 90%, which was significantly greater than the sham burn mortality of 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The value of cerebral angiography in predicting cerebral ischemia during carotid endarterectomy.

OBJECTIVE: Temporary occlusion of the carotid artery during endarterectomy can result in ipsilateral cerebral ischemia if collateral blood flow is insufficient. This requires placement of a shunt across the carotid bifurcation, which is associated with increased operative risk. We retrospectively analyzed preoperative cerebral angiograms and intraoperative electroencephalographic recordings to determine if ischemia during carotid endarterectomy could be predicted from angiographic data. MATERIALS AND METHODS: The cerebral angiograms of 30 patients were examined. Collateral blood flow to the hemisphere on the side of surgery was determined to be present if both proximal segments of the anterior cerebral artery and the anterior communicating artery were visualized, or if filling and washout of the ipsilateral posterior cerebral artery could be seen. Collateral flow was determined to be inadequate if the anterior collateral system was incomplete, and if either the ipsilateral posterior communicating artery was absent or the posterior cerebral artery filled without washout. This information was compared with intraoperative electroencephalographic and shunting data. RESULTS: Of 15 patients who had demonstrable collateral blood flow, 14 had stable electroencephalograms and did not require a shunt during surgery. In all 15 patients in whom no collateral flow to the ipsilateral hemisphere could be shown, electroencephalographic changes prompted placement of an intraluminal shunt. CONCLUSION: We found that the angiographic determination of inadequate collateral cerebral circulation correlated strongly with the development of intraoperative ischemia. This implies that routine preoperative cerebral angiograms can be used to alert the surgeon to the potential need for shunt placement during carotid endarterectomy.

Aged↗
PubMed1991

Evolving experience with thoracoabdominal aortic aneurysm repair at a single institution.

Fifty-seven patients underwent repair of atherosclerotic thoracoabdominal aortic aneurysms between 1978 and 1990. Five patients had urgent surgery for rupture. The 30-day operative mortality rate for the entire group was 18% (10 patients). Before July 1987, 19 patients (group 1) were operated on by use of a technique previously described. In these earlier patients the peritoneum was routinely entered, the diaphragm was divided radially, and no heparin was given. Among patients in group 1 there was a 30-day operative mortality rate of 42% (8 patients), and morbidity included myocardial infarction 4 (21%), respiratory failure 9 (47%), renal failure 12 (63%), bleeding requiring reoperation 4 (21%), and intestinal ischemia 3 (16%). Since July 1987 a standardized approach to all elective thoracoabdominal aortic aneurysms has been used in 38 patients (group 2). This method uses a left thoracoabdominal incision, circumferential division of the hemidiaphragm, retronephric totally extraperitoneal aortic exposure, single lung anesthesia, full heparinization, the graft inclusion technique, and liberal use of visceral endarterectomy. Patients in group 2 sustained a 30-day operative mortality rate of 5% (2 patients) and morbidity included myocardial infarction 2 (5%), respiratory failure 10 (26%), renal failure 11 (29%), bleeding requiring reoperation 1 (3%), paraplegia 6 (16%), and paraparesis 4 (11%). Modern surgery for repair of thoracoabdominal aortic aneurysm results in acceptably low operative mortality rates. Spinal cord ischemia remains an unresolved source of morbidity.

Aged↗
PubMed1991

Femoral-distal bypass with in situ greater saphenous vein. Long-term results using the Mills valvulotome.

During a 7-year period, 440 consecutive in situ saphenous vein grafts originating in the groin were performed in 371 patients, exposing the entire vein for valvulotomy with a modified Mills valvulotome. critical ischemia was the indication for bypass in 68%, and the distal anastomosis was to an infrapopliteal artery in 46%. Thirty-day operative mortality was 2.0%. Postoperative surveillance identified 18 stenotic grafts (4.1%), which were revised while still patent (primary revised patency); 36 grafts (8.2%) underwent revision after graft occlusion (secondary patency). Five-year life-table analysis showed overall primary revised patency of 78%, secondary patency of 83%, limb salvage of 88%, and patient survival of 66%. Femoroperoneal and inframalleolar bypasses fared well. The presence of diabetes did not diminish late graft patency. In contrast to reversed vein grafts, long infrapopliteal in situ grafts had long-term secondary patency similar to shorter femoropopliteal bypass grafts (p greater than 0.05). These results, coupled with the versatility and simplicity of the technique as used in the present series, suggest that in situ vein grafting is the procedure of choice for long infrapopliteal bypass.

Adult↗
PubMed1991

The role of prostaglandin E2 in immune suppression following injury.

It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Limitations of balloon angioplasty for vein graft stenosis.

Vein graft stenosis remains an important contributing factor to the failure of infrainguinal arterial reconstruction. Repair of these lesions before graft occlusion provides sustained patency, yet the optimal method of repair has not been established. Percutaneous transluminal balloon angioplasty of these vein graft lesions has been repeatedly advocated as an alternative to surgical revision. Balloon angioplasty was used in 30 patients with 54 stenotic lesions occurring in autogenous vein grafts after infrainguinal reconstruction. The primary 5-year cumulative patency rate was 18% overall, with no significant differences observed among patency rates based on initial indication, length of stenotic lesion, or requirement for preliminary thrombolytic therapy. The 3-year patency rate associated with vein graft lesions requiring only a single angioplasty proved significantly higher (59%) than those requiring repetitive dilations (6%). It is our conclusion that balloon angioplasty for vein graft stenosis has significant limitations in providing sustained secondary patency.

Adult↗
PubMed1991

Clinical and anatomic considerations for surgery in tibial disease and the results of surgery.

Bypass vein grafts to the infrapopliteal arteries now achieve a 5-year cumulative patency equivalent to that of vein grafts to the popliteal arteries. The technique of in situ vein grafting to the tibial arteries is described and the results are presented. The 5-year cumulative patency for such bypasses and the 5-year limb salvage in the same patients have both been approximately 80%. These results coupled with those reported from other centers that have sizable experience in tibial artery reconstruction suggest that there has been real progress over the past decade in the salvage of lower extremities in patients with far advanced peripheral vascular disease through the use of autogenous venous bypass grafts.

Arteriosclerosis↗
PubMed1990

Effect of low dose recombinant interleukin 2 plus indomethacin on mortality after sepsis in a murine burn model.

Under anaesthesia, 129 8-week-old male A/J mice were subjected to a 25 per cent scald or sham burn and then resuscitated. They were divided at random into two groups. Mice from the first group were allocated into two groups. Mice from the first group were allocated into four subgroups to receive 6 days intraperitoneal (I.P.) injections as follows: (i) recombinant human interleukin 2 (rhIL-2) (250 units day-1); (ii) saline; (iii) indomethacin (5 micrograms-1 day-1); or (iv) rhIL-2 (250 units) + indomethacin (5 micrograms). Sham burned mice served as no treatment controls. All animals were subjected to peritonitis induced by caecal ligation and puncture 10 days after the burn and mortality was assessed. Mice from the second group were allocated to two subgroups to receive 6 days intraperitoneal injections of: (i) rhIL-2 + indomethacin; or (ii) saline. Animals in this group did not undergo septic challenge. They were randomly killed on days 7, 9 or 10 after the burn. Their splenocytes were harvested and assayed for response to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A), and for production of interleukin 2. Mortality rate in animals subjected to burn and septic challenge without treatment was 75 per cent; in mice receiving rhIL-2 alone it was 68 per cent, in mice receiving indomethacin alone it was 62 per cent (no significance) and in mice receiving rhIL-2 + indomethacin it was reduced to 38 per cent (P less than 0.02). Splenocytes from animals receiving combination therapy had markedly improved responses to PHA on days 7 (P = 0.01), 9 (P = 0.02), and 10 (P = 0.008), and to Con A on days 7 (P = 0.001), 9 (P = 0.002) and 10 (P = 0.001), after burn injury. Interleukin 2 production was also significantly (P = 0.004) improved by therapy with rhIL-2 + indomethacin. These data suggest that low dose rhIL-2 in combination with indomethacin may have potential use in the therapy of burn victims.

Animals↗