Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung.

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1 alpha and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s).

An early test of survival in patients with the adult respiratory distress syndrome. The PaO2/FIo2 ratio and its differential response to conventional therapy. Prostaglandin E1 Study Group.

Patients with established adult respiratory distress syndrome (ARDS) have a mortality rate that exceeds 50 percent. We analyzed the magnitude of hypoxemia as manifest by the PaO2/FIO2 ratio and its early response to conventional therapy including positive end-expiratory pressure (PEEP) in the placebo group of a large multicenter study. The PaO2/FIO2 ratio was not different at the time of diagnosis of ARDS in those patients who lived compared to those who subsequently died. After one day of conventional therapy including PEEP, those patients who survived increased their PaO2/FIO2 ratio. The nonsurvivors did not improve over a seven-day course. The difference in the PaO2/FIO2 ratio was significant throughout the seven-day observation period. We conclude that the early response to conventional therapy picks a patient population with a good prognosis and can be used as a test of likely survival from ARDS.

Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.

Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).

Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group.

STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.

Effects of prostaglandin E1 on oxygen delivery and consumption in patients with the adult respiratory distress syndrome. Results from the prostaglandin E1 multicenter trial. The Prostaglandin E1 Study Group.

We wanted to determine the long-term effects of a continuous infusion of PGE1 on DO2 and VO2 in patients with ARDS. Data were obtained from a randomized double-blind multicenter trial, which evaluated the effects of PGE1 on survival in patients with ARDS. Patients were stratified according to treatment and outcome: placebo-died (n = 8); PGE1-died (n = 12); placebo-survived (n = 9); and PGE1-survived (n = 8). In the placebo-died group, elevations occurred in VO2, which were associated with increases in O2ext and a constant DO2. In contrast, in the PGE1-died group, elevations in VO2 were associated with increases in DO2 and an unchanged O2ext. In the placebo-survived group, VO2 and DO2 decreased, whereas in the PGE1-survived group, VO2 and DO2 increased; however, O2ext decreased in both of these groups. Since impaired O2ext occurs in ARDS, PGE1-induced elevations in DO2, rather than compensatory increases in O2ext, may achieve better tissue oxygenation. We conclude that although the recently completed multicenter trial failed to show an enhancing effect of PGE1 on survival in patients with advanced ARDS, PGE1 may have important effects on oxygen transport and, therefore, may still have a role in the treatment of early manifestations of ARDS, either alone or in combination with other agents.

Group rehabilitation for the vascular-disease amputee.

Group therapy for lower-extremity, vascular-disease amputees was successful in the return of these patients to their normal milieu. Thirty men (mean age, 63 years) were studied during a one-year period. The group meetings progressed from a phase of directed therapy to one of nondirected therapy. This group of hospitalized amputees was chosen specifically because of its social, economic and medical identity. After a self-identified adequate period of therapy, all patients returned to their former places in society.

Improving predictive value of complementary tests in carotid artery disease.

In a prospective study the accuracy of B-mode ultrasound imaging alone was compared with its use in conjunction with bidirectional Doppler ultrasound, carotid phonoangiography, and oculoplethysmography to independently assess contrast arteriograms of carotid arteries studied for presumed extracranial vascular disease. The addition of B-mode real-time imaging improved the accuracy of diagnosis by nearly 10%.

When to ambulate the patient with a vascular graft in the groin.

Ankle blood pressure studied pre- and postoperatively in 60 patients after aortofemoral and femoral distal bypass surgery showed no adverse effect after major positional changes (supine, sitting, and standing). Early ambulation was not harmful to graft dynamics in this group of patients.

Value of periangiography hydration.

The value of contrast dye to the planning and evaluation of cardiovascular disease cannot be overestimated. However, adverse renal sequellae may cause the surgeon to hesitate in obtaining an arteriogram, especially in patients with compromised renal function. The purpose of this study was to evaluate the incidence of renal dysfunction in patients requiring angiography. Standard contrast angiography for cerebral or peripheral vascular disease was administered to 150 consecutive patients (89 men and 61 women), with an average age of 63.3 years (range 49 to 89 years). All patients received 100 to 150 ml of dye, with a concentration of approximately 50% iodine. Patients were hydrated with 0.5 N saline/5% dextrose, intravenously, for 8 hours before the procedure (1 to 3 ml/kg/hr). In 31 patients (11 women and 20 men) the serum BUN and/or creatinine levels were elevated (mean BUN value of 48 +/- 9 mg/dl; mean creatinine level of 2.8 +/- 0.6 mg/dl). The patients with abnormal renal function received an additional 300 to 500 ml of intravenous fluid, plus 20 to 40 mg intravenous furosemide, 1 hour before roentgenography to establish a diuresis. All patients were hydrated for 6 hours after angiography with the same solution at the same rate (1 to 3 ml/kg/hr). There were no episodes of compromised renal or cardiopulmonary dysfunction because of contrast angiography. In no patient did the BUN or creatinine level rise, nor was there evidence of acute tubular necrosis, as documented by oliguria and abnormal cells in the urine. Angiography is a safe procedure, even with patients who may have compromised renal function, if appropriate prehydration/posthydration and diuretic measures are undertaken.

Sequelae of limited amputation.

Ninety patients underwent toe amputations because of vascular disease; 21% required higher amputation and 21% healed without further surgery (i.e., revascularization). Of 60 patients who required bypass surgery, 52 underwent successful first amputations and eight required higher amputations. No difference was seen between diabetic and nondiabetic patients in eventual limb salvage; however, men fared better than women. Without bypass surgery, 11 of 30 patients required a higher level of amputation. No patient's toe amputation site healed with an ankle-to-brachial index of less than 0.35. The judicious use of toe amputation remains an important tool in the surgeon's quest for limb salvage.

Hemodynamic assessment of high-compression hosiery in chronic venous disease.

Graded high-compression support hosiery have long been recognized as a physiologically significant mode of therapy for chronic venous disease because of their effects on the hemodynamics of venous return. Photoplethysmography (PPG) in the noninvasive vascular laboratory is now recognized as a quick, simple, and noninvasive measurement technique, which correlates well with ambulatory venous pressure in the postphlebitic limb with chronic venous insufficiency. The purpose of this study was to evaluate the hemodynamic effects, as measured by PPG, of 40 mm Hg graded compression support hosiery in the treatment of patients with a documented history of hospital-treated thrombophlebitis. Fifty lower extremities among 38 patients with a documented history of deep vein thrombosis and chronic venous insufficiency were matched against 50 control extremities among patients without disease. All 50 lower extremities in the study group had abnormal noninvasive venous studies, including Doppler ultrasound examination, phleborheography, and PPG (mean, 5.9. seconds). Thus these patients were ascertained to have incompetent deep venous systems, but with normal arterial flow as documented by ankle:brachial ratios. After application of 40 mm Hg gradient compression stockings to the study group, PPG measurements in all 50 limbs initially converted to normal (20.6 seconds). Abnormal PPG measurements were converted to normal in postphlebitic limbs with the application of graded compression stockings in the 29 patients who wore the prescribed hosiery; 21 patients did not wear the gradient stockings after the initial evaluation(s) and were not found to have improved PPG measurements. It can be concluded that such gradient stockings should be associated with a reduction in ambulatory venous pressure, which may, in turn, lead to clinical prevention or improvement of the various sequelae associated with chronic venous hypertension.

Toe amputation in the diabetic patient.

BACKGROUND: We considered whether it is more practical to amputate the toe of a diabetic patient with osteomyelitis and good circulation or to treat the patient with antibiotics for a prolonged period. METHODS: We undertook a retrospective study of 141 diabetic patients who had undergone a toe-ray amputation for proven or documented osteomyelitis. RESULTS: The mean ankle/brachial index of all patients was 0.81 (range, 0.68 to 1.14); the mean functional days lost on antibiotic therapy was 39 (range, 7 to 84 days). The cost of 6 to 8 weeks of preoperative antibiotic therapy was $900 to $2240 (mean, $1440). CONCLUSIONS: Diabetic patients with good circulation and osteomyelitis of the toe may benefit from prompt toe amputation.

Prostacyclin synthetase activity in diabetic human venous tissue.

The purpose of this study was to ascertain if alterations were present in the prostacyclin synthetase (PGI2ase) activity in diabetic human venous tissue. Saphenous veins were obtained from a group of 12 patients with (HSV-D) or without (HSV-ND) diabetes who were undergoing coronary artery bypass surgery. 14C-Labeled prostaglandin endoperoxide (PGH2) was incubated for 2 minutes with venous microsomal protein. The products were separated by thin-layer chromatography and quantified by radiochromatographic scan. PGI2ase activity was determined by the formation of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin (PGI2). Results of this study indicate the following: both HSV-ND and HSV-D specimens have active PGI2ase and are capable of forming PGI2; there is no difference between PGI2ase activity in HSV-D and HSV-ND specimens; and in diabetes mellitus, any defects in PGI2 production similar to those associated with diabetes in other investigations must reside higher in the arachidonic acid cascade.

Postoperative somnolence in patients after carotid endarterectomy.

Eighty-one patients undergoing carotid endarterectomy were divided into two groups based on the degree of stenosis of the carotid artery. Group I, 37 patients, was defined as having severe carotid stenosis (greater than 70%). Group II, 44 patients, was defined as having mild (less than 40%) or moderate (40% to 70%) carotid artery stenosis. Both groups were evaluated for neurologic and psychologic changes in the postoperative period. Prospective analysis demonstrated no significant differences between groups I and II in the areas of cardiac disease, history of preoperative stroke, preoperative and postoperative hypertension, diabetes, or postoperative computed tomography changes. Group II had a significantly higher percentage of carotid artery ulceration (p less than 0.01). Postoperative analysis revealed 34 group I patients had 6 to 8 weeks of lethargy versus two group II patients (p less than 0.01). Eleven group I patients had headaches for the first week postoperatively versus three patients in group II (p less than 0.05). Four group I patients had paranoid ideation, and another four patients had clinical depression, but not one patient in group II (p less than 0.01) had these psychiatric disturbances. These data suggest that significant, reversible neurologic and psychologic changes can occur because of reperfusion after relief of severe stenosis of the carotid artery.

Gender does not impact infrainguinal vein bypass graft outcome.

BACKGROUND: The percentage of women requiring infrainguinal bypass graft operations continues to increase, whereas the effect of gender on postoperative outcome remains unclear. The purpose of this study was to assess the influence of gender on patient selection and outcome in patients requiring infrainguinal vein bypass grafting procedures. METHODS: This retrospective study reviewed 217 infrainguinal vein bypass grafts performed over an 8-year period. Medical records and patient interviews were used to determine study measures and outcomes. Gender and multiple covariables affecting patient survival were analyzed; postoperative complications and graft patencies were examined. Bivariate and life-table analyses were conducted, followed by multivariate analysis with the Cox proportional hazards model. RESULTS: No statistical differences existed between men and women for age, diabetes, cardiac disease, tobacco use, hypertension, stroke, renal disease, or prior contralateral bypass or major amputation. Women were more likely to be black (P =.014) and have a spliced vein graft (P =.035). No differences were noted between the 2 groups for 30-day morbidity rates-except women had more incisional complications (P =.01)-or for survival (P =.45), primary-patency (P =.57), secondary-patency (P =. 79), or limb-salvage rates (P =.40). Multivariate analysis showed that gender had no role in affecting survival rates. CONCLUSIONS: Gender does not affect graft patency, limb salvage, or survival rates. There should be no introduction of a gender bias into management of infrainguinal occlusive disease.

Septic pelvic thrombophlebitis: an update.

Septic pelvic thrombophlebitis is the result of serious pelvic infection usually following obstetric or gynecologic procedures. The management of this condition is of historical interest to the department of obstetrics and gynecology at Tulane, and therefore a retrospective case evaluation and a prospective surveillance were undertaken. This study indicates that septic pelvic thrombophlebitis is seen very rarely today. Possible reasons for the decline in the incidence of this problem and a management plan are presented. Three cases are included.

Pulmonary dysfunction associated with streptokinase therapy.

A 66-year-old lower-extremity amputee with an acute femoral artery occlusion was treated with low-dose (10000 units/h) percutaneous constant-infusion streptokinase. At 48 hours after initiation of therapy, the patient experienced adult respiratory distress syndrome and died. A postmortem examination confirmed the diagnosis; laboratory studies reflected an increased level of fibrinolytic split products, thrombocytopenia, and a low level of fibrinogen.

Successful thrombolytic therapy for acute and chronic occlusion of polytef vascular grafts.

Thrombolytic therapy for thrombosed arterial bypass grafts has received little attention in the medical literature. We carried out successful thrombolysis in occluded polytef arterial bypass grafts. A femoral-femoral artery crossover graft had been occluded 13 days, and a femoral-popliteal artery bypass graft had been occluded three months. No surgical intervention was required. Follow-up showed continued patency nine months following thrombolytic therapy. Long-term oral anticoagulation seems indicated. Also, data suggest thrombus in polytef grafts may be particularly susceptible to lyses. Thrombolytic therapy should play an increasing role in vascular surgery.

Serosal tears following colonoscopy.

After colonoscopic perforation, laparotomy was performed in a 28-year-old woman. Seromuscular tears and lacerations were found in an adjacent loop of sigmoid colon that appeared normal through the colonoscope. At laparotomy, the mucosa of that loop was entirely intact. Six weeks later, a laparotomy was again performed, revealing well-healed lacerations with extensive adhesion formation. The incidence of this complication in patients undergoing colonoscopy is unknown.

Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing.

HYPOTHESIS: In patients with diabetic foot and pressure ulcers, early intervention with biological therapy will either halt progression or result in rapid healing of these chronic wounds. DESIGN: In a prospective nonrandomized case series, 23 consecutive patients were treated with human skin equivalent (HSE) after excisional debridement of their wounds. SETTING: A single university teaching hospital and tertiary care center. PATIENTS AND METHODS: Twenty-three consecutive patients with a total of 41 wounds (1.0-7.5 cm in diameter) were treated with placement of HSE after sharp excisional debridement. All patients with pressure ulcers received alternating air therapy with zero-pressure alternating air mattresses. MAIN OUTCOME MEASURE: Time to 100% healing, as defined by full epithelialization of the wound and by no drainage from the site. RESULTS: Seven of 10 patients with diabetic foot ulcers had complete healing of all wounds. In these patients 17 of 20 wounds healed in an average of 42 days. Seven of 13 patients with pressure ulcers had complete healing of all wounds. In patients with pressure ulcers, 13 of 21 wounds healed in an average of 29 days. All wounds that did not heal in this series occurred in patients who had an additional stage IV ulcer or a wound with exposed bone. Twenty-nine of 30 wounds that healed did so after a single application of the HSE. CONCLUSIONS: In diabetic ulcers and pressure ulcers of various durations, the application of HSE with the surgical principles used in a traditional skin graft is successful in producing healing. The high success rate with complete closure in these various types of wounds suggests that HSE may function as a reservoir of growth factors that also stimulate wound contraction and epithelialization. If a wound has not fully healed after 6 weeks, a second application of HSE should be used. If the wound is not healing, an occult infection is the likely cause. All nonischemic diabetic foot and pressure ulcers that are identified and treated early with aggressive therapy (including antibiotics, off-loading of pressure, and biological therapy) will not progress.