Biomedical subjects

J A Mannick

Publications and source records attributed to J A Mannick.

At least 55 records · Page 3Linked to original sources

PubMed1995

Preferred strategies for secondary infrainguinal bypass: lessons learned from 300 consecutive reoperations.

PURPOSE: To determine the optimal surgical strategies in reoperative infrainguinal bypass, we reviewed our results in 300 consecutive secondary bypasses in 251 patients operated on between Jan. 1, 1975, and Nov. 1, 1993. METHODS: There were 168 men (67%) and 83 women (33%), with a mean age of 64.8 years and a typical distribution of risk factors including smoking (76.4%), diabetes (33.7%), and coronary artery disease (47.1%). The indications for surgery were limb-threatening ischemia in 83.5% and severe claudication in 16.5% of patients. The majority of conduits (n = 213) were autogenous vein and were composed of a single segment of greater saphenous vein in 121 bypasses (57%) and various alternative veins including composite, arm, and lesser saphenous vein in 92 bypasses (43%). Prosthetic conduits included 69 polytetrafluoroethylene, 16 umbilical vein, and two Dacron grafts. RESULTS: There was one perioperative death (0.3%) and a 25% total morbidity rate including a 1.7% myocardial infarction rate. There was a 28.6% early (< 30 days) graft failure and 10.7% early amputation rate for prosthetic bypass grafts compared with 13.6% early graft failure and 5.6% early amputation rates for vein grafts. Autogenous vein bypasses had higher 5-year secondary patency rates than had prosthetic grafts (51.5% +/- 4.6% vs 27.4% +/- 6.1%, p < 0.001). Results with autogenous vein bypass improved significantly from the 1975 to 1984 to the 1985 to 1993 interval with 5-year secondary patency rates increasing from 38.3% +/- 6.9% to 59.1% +/- 5.8% (p = 0.017) and 5-year limb-salvage rates increasing from 40.4% +/- 7.6% to 72.4% +/- 6.6% (p < 0.001). Vein grafts to the popliteal and tibial outflow levels had equivalent long-term results. Vein grafts completed for claudication demonstrated results superior to those for limb salvage, with a 5-year secondary patency rate of 75.8% +/- 8.1% versus 52.3% +/- 7.9% (p = 0.048). Secondary autogenous vein bypass grafting performed after early primary graft failure (< 3 months) did particularly poorly, with only a 27.2% +/- 7.7% 4-year secondary patency rate. Greater saphenous veins tended to perform better than alternative vein bypasses, with a 5-year secondary patency rate of 68.5% +/- 6.0% compared with 48.3% +/- 10.5% (p = 0.09) and a 5-year limb-salvage rate of 77.8% +/- 7.4% versus 54.2% +/- 11.8% (p = 0.046). CONCLUSIONS: When patients suffer a recurrence of limb-threatening ischemia at the time of infrainguinal graft failure, aggressive attempts at secondary revascularization with autogenous vein are warranted based on the low surgical morbidity and mortality rates and the improved patency and limb salvage rates that are currently attainable.

Amputation, Surgical↗

PubMed1995

Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection.

OBJECTIVE: Patients with serious traumatic injury and major burns and an animal model of burn injury were studied to determine the effect of injury on the production of cytokines typical of the T helper-2 lymphocyte phenotype as opposed to the T helper-1 phenotype and on the production of interleukin-12. SUMMARY BACKGROUND DATA: Perturbations of natural and adoptive immunity are related to the increased susceptibility to infection manifested by seriously injured and burn patients. Earlier work has shown that impaired adoptive immunity after injury is characterized by diminished production of interleukin-2 (IL-2), a product of Th lymphocytes. Exposure of naive Th cells to certain antigens and cytokines causes conversion to either the Th-1 or the Th-2 phenotype. Th-1 cells produce IL-2 and interferon-gamma (IFN-tau) and initiate cellular immunity. Th-2 cells secrete interleukin-4 (IL-4) and interleukin-10 (IL-10) and stimulate production of certain antibodies. Conversion to the Th-1 phenotype is facilitated by IL-12, and conversion to the Th-2 phenotype is promoted by IL-4. The authors believed that serious injury might cause conversion of Th cells to the Th-2 as opposed to the Th-1 phenotype rather than generalized Th suppression. METHODS: The authors studied circulating peripheral blood mononuclear cells (PBMC) from 16 major burn and 8 trauma patients on 32 occasions early after injury and from 13 age- and sex-matched healthy individuals for cytokine production after phytohemagglutinin stimulation. Also studied was a mouse model of 20% burn injury known to mimic the immune abnormalities seen in humans with burns. Splenocytes from burn mice, 10 to 12 per group, were studied after activation by concanavalin A or by the bacterial antigen Staphylococcus aureus Cowan strain I for cytokine production and cytokine messenger RNA expression as determined by reverse transcriptase polymerase chain reaction. Burn mice were compared with sham-burn controls and attention was focused on day 10 after burn injury, a time when IL-2 production and resistance to infection are highly suppressed. Finally, burn and sham-burn animals, 20 per group, were treated in vivo with IL-12 (25 ng daily for 5 days) and observed for mortality after septic challenge (cecal ligation and puncture [CLP]) performed on day 10 after injury. RESULTS: Peripheral blood mononuclear cells from burn and trauma patients produced less IFN-tau, the index cytokine of Th-1 cells, than PBMCs from healthy individuals 1 to 14 days after burn injury (SE = 77.6 +/- 16 pg/mL patients vs. 141.3 +/- 35 pg/mL controls, p < 0.05). However, production of IL-4, the index cytokine of Th-2 cells, by patient PBMCs was increased (51.0 +/- 13.0 pg/mL patients vs. 26.9 +/- 2.5 controls, p < 0.05). Splenocytes from mice 10 days after burn injury, when compared with sham-burn controls, showed diminished production of IL-2 (1.04 +/- 0.91 units/mL burns vs. 5.8 +/- 0.55 units/mL controls, p < 0.05) and IFN-tau (1.05 +/- 0.7 units/mL burns vs. 12.0 +/- 8.9 units/mL controls, p < 0.05). However, burn splenocytes produced more IL-4 (2492 +/- 157.0 pg/mL burns vs. 672.0 +/- 22.7 pg/mL controls, p < 0.01) and IL-10 (695.2 +/- 20.8 pg/mL burns vs. 567.0 +/- 16.7 pg/mL controls, p < 0.05). Splenocyte production of IL-12 was also reduced after burn (0.20 +/- 0.035 units/mL) as compared with sham burn (0.46 +/- 0.08 units/mL, p < 0.05). The reduction in IL-2, IFN-tau, and IL-12 production by burn splenocytes was reflected by a tenfold decrease in expression of their respective cytokine mRNAs. In vivo IL-12 treatment of burn animals decreased mortality from CLP on day 10 after injury from 85% to 15% (sham-burn mortality after CLP, 15%, p < 0.05) and increased splenocyte IFN-tau production to supranormal levels. CONCLUSIONS: Serious injury induced diminished production of IL-1 2 and a shift to the Th-2 phenotype with increased production of IL-4 and IL-10, cytokines known to inhibit Th-1 function. The ability of exogenous IL-12 to restore Th-1 cytokine production and resistance to infection suggests a therapeutic role for IL-12 in the immune dysfunction seen after major injury.

Adult↗

PubMed1995

Long-term immunotherapeutic intervention with pentoxifylline in a mouse model of thermal injury and infection.

Major thermal or traumatic injury often results in abnormalities of immune function, and these abnormalities contribute to the increased susceptibility to infection observed in these patients. Abnormalities of T-cell function, including decreased proliferation and secretion of cytokines are observed following major injury and, conversely, there is markedly increased monokine production. Thus, therapy of this syndrome might logically be aimed at modulating the immune system to upregulate T-cell function and downregulate monocyte hyperactivation. Pentoxifylline (PTX), a methylxanthine derivative, has been shown to be therapeutically effective in several animal models. The purpose of this study was to evaluate PTX and its effect on cytokine production in a mouse model of thermal injury and to study its effect on survival after septic challenge. The results show that PTX therapy after injury can restore T-cell production of IL-2 and downregulate the hyperactive macrophage secretion of proinflammatory cytokines. However, improvement in survival resulting from this therapy following thermal injury and septic challenge depends on timing of dosage.

Animals↗

PubMed1995

Multiple system organ failure may be influenced by macrophage hypoactivation as well as hyperactivation--importance of the double challenge.

OBJECTIVE: To find out if an infective challenge caused by a burn followed by caecal ligation and puncture in mice caused more abnormalities of the immune response than burn alone or caecal ligation and puncture alone. DESIGN: Laboratory study. SETTING: University hospital, USA. MATERIAL: 80 male 7-8 week old A/J mice. INTERVENTIONS: Burn followed 10 days later by caecal ligation and puncture (n = 18), caecal ligation and puncture alone (n = 24), burn alone (n = 20), and controls (n = 18). The mice had their spleens removed on day 11 (n = 28; 6, 8, 8, and 6 in the respective groups), day 12 (n = 26; 6, 8, 6, and 6), and day 13 (n = 26; 6, 8, 6, and 6), and splenocytes and adherent cells were harvested for measurement of prostaglandin E2 (PGE2), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha). MAIN OUTCOME MEASURES: Alterations in the production of the cytokines. RESULTS: After the double challenge (burn followed by caecal ligation and puncture) there were significant reductions in production of TNF-alpha and IL-6 compared with caecal ligation and puncture alone (p < 0.05), burn alone (p < 0.05), and controls (p < 0.05). These findings indicate that activation of macrophages was reduced after infection; production of TNF-alpha, IL-1, and IL-6 by splenocytes stimulated by lipopolysaccharide was reduced. CONCLUSIONS: The differences do not seem big enough to indicate that mortality would be increased after caecal ligation and puncture alone. Only when there has been a previous injury (which resulted in hyperactivation of macrophages followed by a more pronounced hypoactivation) would mortality increase. In view of clinical trials with antiendotoxin and antiTNF antibodies that failed to improve survival in infected patients, we suggest that the mechanisms of the cellular immune response need further clarification.

Animals↗

PubMed1994

The role of cyclic adenosine monophosphate in the suppression of cellular immunity after thermal injury.

BACKGROUND AND OBJECTIVE: Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is known to convey inhibitory signals for T-cell proliferation and function. We investigated the association between this molecule and the profound immunosuppression that accompanies thermal injury. DESIGN: Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E2 (PGE2). RESULTS: Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P < .05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE2 resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane-associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H-8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury. CONCLUSIONS: These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE2, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation.

Animals↗

PubMed1994

Randomized prospective study of angioscopically assisted in situ saphenous vein grafting.

PURPOSE: A study was conducted to test the hypothesis that angioscopically assisted valve lysis and vein branch identification during in situ saphenous vein bypass would reduce technical causes of graft failure, local operative morbidity, and hospital stay. METHODS: Patients requiring primary bypass to an infrageniculate artery were randomly assigned to undergo in situ saphenous vein bypass with valvulotomy and branch identification either under angioscopic visualization with use of short intermittent incisions (scope) or under direct vision with use of a continuous incision (no scope). Data on operative details, morbidity, hospital length of stay, and graft patency were collected prospectively and compared. RESULTS: Fifty-nine patients were enrolled (32 scope, 27 no scope). There were no significant differences between study groups in the incidence of diabetes, claudication versus critical ischemia indications for surgery, or popliteal versus infrapopliteal location of distal anastomoses. Rates of wound complications (9.3% and 3.7%), early graft occlusion (6.2% and 7.4%), and mean postoperative hospital stay (8.0 and 8.6 days) were statistically similar for the scope and no scope groups, respectively. Differences in cumulative secondary patency rates at 48 months (79% scope, 91% no scope) were also insignificant. CONCLUSIONS: Use of angioscopy to assist with preparation of the in situ vein for infrageniculate grafting appears to have no impact on local operative morbidity, hospital length of stay, or midterm graft patency.

Aged↗

PubMed1994

Does the route of feeding modify the inflammatory response?

OBJECTIVE: The authors compared the responses to endotoxin in enterally and parenterally fed human volunteers. BACKGROUND: Recent investigations have reported that the response to endotoxin in humans is greater in individuals who receive parenteral nutrition rather than enteral feeding. It was proposed that this difference was related to gut barrier dysfunction during intravenous nutrition. To evaluate this hypothesis, the authors analyzed the responses of human subjects to an intravenously administered bolus of endotoxin after enteral or parenteral nutrition. METHODS: Fifteen randomly selected healthy volunteers were studied during two separate investigations; ten studies were performed in ten subjects who received enteral nutrition, and nine studies were carried out in five additional subjects who received parenteral nutrition. After 2 days of enteral feedings or 7 days of parenteral feedings, endotoxin was administered by intravenous injection; temperature, symptom score, and duration then were measured serially. Blood samples were obtained for leukocyte and platelet count, and plasma concentrations of corticotrophin, cortisol, epinephrine, norepinephrine, tumor necrosis factor, and interleukin-6. Mononuclear cell response to phytohemagglutinin was determined at 0, 4, and 24 hours. RESULTS: In the parenteral group, a diminished response was observed in platelet count and plasma interleukin-6 levels compared with volunteers who received enteral nutrition. The duration of symptoms tended to be reduced in the parenterally fed group, although this did not achieve significance. Other responses were not significantly different between the two groups. CONCLUSION: The responses to endotoxin in human subjects who received parenteral nutrition were similar compared with subjects who received enteral nutrition, although platelet count and plasma interleukin-6 concentration were diminished.

Adrenocorticotropic Hormone↗

PubMed1994

Altered gene transcription after burn injury results in depressed T-lymphocyte activation.

OBJECTIVE: Patients with major burns and an animal model of burn injury were studied to determine the mechanism of depressed interleukin-2 (IL-2) production after thermal injury and to determine the effect of such injury on IL-2 receptor (IL-2R) expression and function. SUMMARY BACKGROUND DATA: Major burn injury is known to diminish resistance to infection by altering cytokine production and prostanoic secretion and by inhibiting T-lymphocyte activation. T-cell activation requires production of regulatory cytokines, principally IL-2, and expression of the appropriate cytokine receptors. Depressed IL-2 production after major burn injury is undisputed, although the molecular mechanisms remain undefined; the effect of burn injury on IL-2R expression and function currently is controversial. METHODS: The authors studied serial samples of peripheral blood mononuclear cells (PBMC) from 11 patients with 25% to 95% surface area burns and 7 age-matched volunteer control subjects. Peripheral blood mononuclear cells were stimulated by the T-cell mitogen phytohemagglutinin (PHA), and IL-2 production and mRNA expression by Northern blot were determined. Expression and function of IL-2R were determined by monoclonal antibodies to the p55 and p75 chains of the IL-2R, binding of fluorescein-labeled IL-2, and response to exogenous recombinant IL-2. We also studied a mouse model of 20% burn injury known to mimic the immune abnormalities seen in humans with burns. Splenocytes from mice with burns (20-22 per group) were studied for IL-2 production and IL-2 mRNA expression after stimulation with the T-cell mitogen concanavalin A (ConA) and compared with sham burn control subjects. Kinetics of mRNA expression after ConA stimulation also were determined and a nuclear run-on assay performed to determine IL-2 gene transcription. The mRNA expression was determined for the proto-oncogenes c-jun and c-fos, whose protein products join to form transcription factor AP1, which is necessary for activation of the IL-2 promoter. Splenocytes from mice with burns after ConA stimulation also were studied for expression and function of the IL-2R. RESULTS: Peripheral blood mononuclear cells from burn patients compared with healthy control subjects showed diminished (p < 0.05) IL-2 production and mRNA expression 4 to 10 days after burn injury. Burn PBMC demonstrated normal expression of IL-2R, p55, and p75 chains 0 to 7, 8 to 20, and 21 to 37 days after burn injury, normal IL-2R binding of fluorescein-labeled IL-2, and a normal proliferative response to PHA in the presence of exogenous recombinant IL-2. Splenocytes from mice 7 days after burn injury showed diminished production (p < 0.05) of IL-2 and IL-2 mRNA expression after ConA stimulation as compared with sham burn control subjects. Kinetics of mRNA expression after ConA stimulation were the same for burn and control mice, indicating that reduced IL-2 mRNA expression was not caused by altered mRNA degradation. A nuclear run-on assay confirmed decreased IL-2 gene transcription in burn splenocytes. Burn splenocytes showed normal expression of mRNA for c-jun but diminished expression of mRNA for c-fos. Finally, splenocytes from mice with burns after ConA stimulation showed normal expression and function of the IL-2R 7, 10, 14, and 21 days after burn injury. CONCLUSIONS: These human and animal studies indicate that major burn injury depresses T-cell activation at the level of IL-2 gene transcription at least in part by inhibiting c-fos expression, whereas IL-2R expression and function remain normal and T-cell proliferation can be restored to normal levels by exogenous IL-2.

Adult↗

PubMed1994

The humoral immune response after thermal injury: an experimental model.

BACKGROUND: Severe thermal injury is associated with major alterations in cell-mediated immunity. Because most B-cell responses are regulated or critically dependent on T-cell help, it is not surprising that many studies have also shown a variety of defects in humoral immunity after thermal injury. However, the nature of the relationship between the in vitro ability to produce antibody and subsequent in vivo responses remains unclear. METHODS: With a murine model of thermal injury, the primary and secondary humoral immune response to tetanus toxoid (TT) was examined during a 6-week period after sham burn or burn injury. Serum anti-TT titers and the numbers of anti-TT-secreting splenocytes were determined. RESULTS: Splenocytes from burned animals displayed normal or decreased TT-specific immunoglobulin (Ig) M plaque formation. In contrast, however, IgG plaque formation was persistently increased for up to 6 weeks after thermal injury, suggesting a switch from IgM to IgG antibody production. Conversely serum titers of TT-specific IgG antibody were persistently lower in burn, compared with sham groups. Changes in serum immunoglobulin levels did not account for this marked discrepancy between enhanced in vitro IgG plaque formation but impaired in vivo levels of TT antibody. CONCLUSIONS: The data suggest that thermal injury is associated with a diminished ability to propagate and maintain a normal IgG antibody response, despite the presence of normal or increased numbers of antigen-specific B cells.

Animals↗

PubMed1993

Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin.

Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.

Animals↗

PubMed1993

Glutathione depletion in rats impairs T-cell and macrophage immune function.

Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.

Animals↗

PubMed1993

Cytokines, sepsis and immunomodulation.

Tissue injury and infection produce significant alterations in host metabolic and immune homeostasis. It is increasingly clear that many of these changes result from a complex cascade of mononuclear phagocyte-derived endogenous mediators. Among the more important is a group of host proteins called cytokines, which play an integral role in mediating the host response to tissue injury and infection. Of these proteins, tumour necrosis factor (TNF) and interleukin (IL) types 1 and 6 have received much attention for their pathophysiological roles in infection and trauma. Evidence is reviewed for the involvement of these cytokines in the characteristic alterations in the metabolic and immune responses to such injury. These endogenous mediators initiate an integrated fuel substrate and hormonal adjustment to trauma and sepsis, and help to provide optimal metabolic homeostasis for systemic host defences. Widespread tissue injury, especially when associated with fulminant sepsis, may, however, precipitate massive release of TNF, IL-1 and IL-6, triggering a series of reactions involving multiple organs, and culminating in the 'sepsis syndrome'. New therapies designed to downregulate this aberrant response, either by neutralizing endotoxin directly or by blocking the release or actions of these cytokines, are reviewed. Although these treatments hold much promise for the future management of severely traumatized and infected patients, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended.

Humans↗

PubMed1993

Lymphokine activated killer cells enhance IL-2 prevention of sepsis-related death in a murine model of thermal injury.

It has previously been shown by this laboratory that immunomodulation of thermally injured animals with low-dose interleukin-1 (IL-2) and indomethacin (Indo) improves survival following septic challenge. Lymphokine-activated killer (LAK) cells have been shown to be effective in certain viral infections and to act in synergy with IL-2 in the treatment of certain types of cancer. We have studied the effect of LAK cells in combination with IL-2 and Indo in a murine model of thermal injury and sepsis. Male A/J mice received a 25% scald burn injury or sham burn and were randomized into five groups: (a) sham/vehicle, (b) burn/vehicle, (c) burn/IL-2 (250 U) + Indo (5 micrograms), (d) burn/LAK cells (2 x 10(6) cells), or (e) burn/LAK cells+IL-2+Indo and were treated accordingly for 6 days following injury. LAK cells were generated by in vitro IL-2 treatment of syngeneic spleen cells for 72 hr and cytotoxic activity was confirmed by standard 51Cr release assay using natural killer (NK)-sensitive and NK-resistant targets. In the groups receiving LAK cells they were administered on Day 1 and Day 6 postinjury. On Day 10, septic challenge by cecal ligation and puncture (CLP) or splenectomy, for in vitro studies, was performed. Five-day survival after CLP was 80% in the sham/vehicle group compared to 0% in the burn/vehicle group (P < 0.01). IL-2/Indo and LAK/IL-2/Indo improved survival to 25% (P < 0.05) and 57.1% (P < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Further experience with an all-autogenous tissue policy for infrainguinal reconstruction.

PURPOSE: Between 1985 and 1991 a policy of strong preference for autogenous methods of infrainguinal reconstruction was followed to assess the efficacy of this strategy. METHODS: A total of 585 autogenous infrainguinal reconstructions were performed on 537 limbs in 448 patients between 1985 and 1991. Thirty-eight additional revascularizations were performed with prosthetic materials and seven patients underwent primary amputation during this interval. Of the autogenous reconstructions, 74% were primary and 26% were secondary procedures, 71% were for limb salvage, and 48% were to infrapopliteal arteries. Greater saphenous vein was used for 447 bypass grafts. Other autogenous methods included bypass with lesser saphenous (21), arm (20), and composite (30) veins, endarterectomy of the common femoral (18) and superficial femoral (40) arteries, and isolated profundaplasty (9). RESULTS: Major operative morbidity occurred in 41 patients (7%), early graft failure in 47 (8%), and death in 12 (2%). At 5 years, the overall cumulative primary patency rate was 63% and the secondary patency rate was 72%. The 5-year secondary patency rate for the subgroup in which greater saphenous vein was used was 79% and for alternative autogenous methods the rate was 49% (p < 0.001). During the period of follow-up, major amputation was performed in 45 (7.9%) of the operated limbs. CONCLUSION: This experience supports continued preferential use of autogenous methods for infrainguinal reconstruction.

Adult↗

PubMed1993

Infrainguinal reconstruction for patients with chronic renal insufficiency.

PURPOSE: The efficacy of autogenous infrainguinal reconstruction for patients with varying degrees of chronic renal insufficiency was reviewed because it has not been well defined. METHODS: Pertinent data were retrieved from hospital records and the vascular registry for all patients with chronic renal insufficiency (serum creatine > 2 mg/dl) who required surgical intervention for ischemic lower limbs during the past 15 years at Brigham and Women's Hospital. RESULTS: During the past 15 years, 56 patients underwent 70 autogenous vein bypass procedures, and 31 underwent 42 primary major amputations. All patients had serum creatinine levels greater than 2 mg/dl. Limb salvage was the indication for intervention in 84% of reconstructed limbs, and 48% required infrapopliteal bypass. No significant difference was found in the operative mortality rate associated with primary amputation (17%) and reconstruction (11%), but overall 5-year survival for the group undergoing reconstruction (40%) was significantly superior to that observed in the group undergoing amputation (9%). The 5-year cumulative limb salvage rate for the group having reconstruction was 80%, with a primary graft patency of 74% and a secondary patency of 77%. Patients with diabetes had lower rates of both limb salvage (63%) and survival (21%). No patient on dialysis survived beyond the third-year interval, but the limb salvage rate after 2 years was 76%. CONCLUSION: Patients with chronic renal insufficiency achieved graft patency and limb salvage results comparable to those obtained in patients with normal kidney function, but they sustained higher perioperative morbidity and reduced survival.

Adult↗

PubMed1993

Impact of completion angiography on operative conduct and results of carotid endarterectomy.

OBJECTIVE: This study assessed the impact of operative completion angiography on conduct and results of carotid endarterectomy (CEA). SUMMARY BACKGROUND DATA: Completion imaging by angiography, ultrasound or angioscopy reveals occasional residual lesions after CEA. The importance and appropriate management of these lesions remain controversial with respect to operative morbidity and long-term restenosis. METHODS: Carotid endarterectomy was performed 410 times for transient ischemic attack (44%), amaurosis fugax (19%), prior stroke (10%), and asymptomatic carotid stenosis (27%). Routine intraoperative completion angiograms were obtained to exclude significant residual lesions. Postoperative ultrasound follow-up was obtained in 232 patients over a mean interval of 17.3 months. RESULTS: Angiography revealed 71 defects warranting correction in 66 cases (16.1%), including kinks (23), external carotid flaps (18), common carotid plaque (10), thrombus (10), distal internal carotid stenosis (8), intracranial occlusion (1), and spasm (1). Operative morbidity included seven ipsilateral strokes (1.7%) and operative mortality was 0.7%. During follow-up, restenosis > 80% was detected in 17 (7.3%) of 232 arteries, 9 (3.9%) of which underwent reoperation. Rates of restenosis of > 80% were similar between sexes and patched versus unpatched arteries. CONCLUSIONS: Routine completion angiography after CEA guides use of selective operative revision contributing to low rates of perioperative morbidity and restenosis.

Adult↗

PubMed1993

Carotid endarterectomy: preoperative evaluation of candidates with combined Doppler sonography and MR angiography. Work in progress.

Doppler sonography and magnetic resonance (MR) angiography were prospectively used in combination as a substitute for conventional angiography in 24 consecutive patients likely to undergo carotid endarterectomy. Of 19 patients (20 lesions) who underwent carotid endarterectomy, 18 had not undergone preoperative angiography. High-grade lesions (> 75%-diameter stenosis) were surgically confirmed in 16; a 60%-70% stenosis, in one; and subtotal occlusion of the internal carotid artery, in another. Angiography was performed in a case of suspected internal carotid artery dissection. In the five nonsurgical cases, no significant stenosis was noted with both techniques in two instances, total occlusion was seen in two cases, and an asymptomatic stenosis was seen in one. Follow-up (average, 4.5 months) showed one case of symptomatic occlusion of the internal carotid artery after endarterectomy. This preliminary study suggests that the combined use of Doppler sonography and MR angiography can, in up to 79% (15 of 19) of cases, replace angiography for the preoperative evaluation of patients likely to need carotid endarterectomy.

Aged↗

PubMed1993

Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion.

A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01).

Aged↗