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Biomedical subjects

G J Slotman

Publications and source records attributed to G J Slotman.

At least 73 records · Page 4Linked to original sources

Thromboxane A2 mediates hemodynamic and respiratory dysfunction in graded bacteremia.

Thromboxane A2 has been implicated as a mediator of cardiorespiratory dysfunction in sepsis. This study evaluated whether or not thromboxane A2 was necessary or sufficient for these adverse effects to occur during bacteremia. Fourteen adult swine under barbiturate anesthesia and breathing room air were monitored with arterial and pulmonary artery catheters. Animals were studied for 4 hours in three groups: group I, graded infusion of 10(9)/ml Aeromonas hydrophila; group II, Aeromonas hydrophila infusion plus SQ 29,548 (thromboxane A2 antagonist); and group III, U46619 (thromboxane A2 agonist) infusion in normal swine to pulmonary artery pressures observed in group I. Hemodynamic parameters, arterial and mixed venous blood gases, and plasma thromboxane B2 and prostaglandin 6-keto-F1 were measured. At sacrifice after 4 hours, wet-to-dry lung weights were calculated. Results indicated that thromboxane A2 was necessary and sufficient for the development of pulmonary hypertension and impaired alveolar-capillary oxygen diffusion in graded bacteremia. It was necessary but not sufficient for increased lung water to occur and sufficient but not necessary for decreased cardiac index and stroke volume index. Thromboxane A2 was neither sufficient nor necessary to the pathophysiology of systemic hypotension during graded bacteremia. Plasma prostaglandin 6-keto-F1 levels were increased in hypotensive animals with sepsis, suggesting its involvement in hypotension during sepsis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Prostacyclin and thromboxane A2 in septic shock: species differences.

Prostacyclin and thromboxane A2 have been implicated as mediators of septic shock. Correlations between the human prostanoid response to sepsis and experimental paradigms are poorly understood. The purpose of this study was to compare changes in plasma levels of prostaglandin 6-keto-F1 alpha (PGI) and thromboxane B2 (TxB) during septic shock in Sprague-Dawley rats, domestic pigs, mongrel dogs, and man. Severe sepsis followed by septic shock (systolic BP less than 90 mmHg) was induced in rats by inoculation of 1.0 X 10(9) Aeromonas hydrophila, in pigs by graded IV infusion of 1.0 X 10(9)/ml A. hydrophila; and in dogs by an IV bolus injection of 5.0 X 10(9)/ml Escherichia coli. Plasma PGI and TxB (pg/ml) were measured by radioimmunoassay in control, septic, and septic shock experimental blood samples, and in normal controls, severly septic, and septic shock (systolic BP less than 90 mmHg) S.I.C.U. patients. Control, septic, and septic shock TxB levels in the dog and the pig were significantly greater than in the rat and man. PGI levels in the dog were significantly greater than in other species. TxB increased significantly in murine sepsis and PGI increased significantly in sepsis and septic shock. TxB increased during porcine sepsis and septic shock. In man, both PGI and TxB were significantly increased in severe sepsis, compared to normal controls, but only PGI was significantly higher in septic shock versus normotensive sepsis. Patterns of change in TxB/PGI ratios were similar for all species studied. Changes in PGI in the porcine septic experiments most closely paralleled those observed clinically.

Animals↗

Enterobacter bacteremia in surgical patients.

The records of 63 surgical patients with one or more positive blood cultures for Enterobacter organisms were reviewed to determine clinical, epidemiologic, and mortality risk factors. Enterobacter bacteremia occurred, on the average, on the twenty-third day of hospitalization, most frequently in male patients (47), after antibiotic therapy (48 patients), placement of central venous catheters (38 patients), gastrointestinal tract operations (36 patients), and respiratory failure (31 patients). Portals of entry were most commonly sputum (25 patients), open skin wounds (16 patients), and central venous lines (12 patients). Mortality risk (22 patients, 35%) was increased with Enterobacter bacteremia occurring after the fifteenth day of hospitalization (18 of 45 patients versus 4 of 28 patients, p less than 0.01), a preceding Enterobacter focus (13 of 22 patients versus 9 of 41 patients, p less than 0.05), preceding non-Enterobacter bacteremia (10 of 15 patients versus 12 of 48 patients, p less than 0.02), preceding total parenteral nutrition (11 of 21 patients versus 11 of 42 patients p less than 0.01), respiratory failure (19 of 36 patients versus 3 of 27 patients p less than 0.01), and renal failure (11 of 12 patients versus 11 of 51 patients p less than 0.01). The mortality risk was not diminished by specific antibiotic therapy. Enterobacter is emerging as an important pathogen in surgical patients. Prolonged antibiotic administration, particularly that of cephalosporins, may promote Enterobacter colonization of the tracheobronchial tree and skin with subsequent invasion enhanced by respiratory failure, open skin wounds, or central venous catheters traversing the skin. Mortality risk is determined primarily by factors associated with critical illness rather than effects of Enterobacter organisms and their specific treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗

Enterococcal bacteremia in surgical patients.

In 73 surgical patients enterococcal bacteremia was preceded by antibiotic administration (n = 58), central venous catheters (n = 52), other-organism bacteremia (n = 44), and gastrointestinal tract operations (n = 41). Surgical wounds and urinary tract infections were the most frequent portal of entry. The overall mortality was 42%. The mortality risk was significantly greater in patients with preceding or concomitant gram-positive bacteremia and four or more days of cephalosporin administration prior to enterococcemia. In 21 patients who had been given cephalosporins and who had gram-positive bacteremia, specific antienterococcal therapy resulted in survival in five of nine patients, compared with three of 12 who survived without therapy. Enterococcal bacteremia in surgical patients follows antibiotic administration, central venous catheter use, other-organism bacteremia, and intra-abdominal operations. Preceding or concomitant gram-positive bacteremia defines a subgroup of patients with high mortality who seem to respond to antienterococcal therapy.

Adult↗

Thromboxane and prostacyclin in clinical acute respiratory failure.

Plasma levels of thromboxane A2 and prostacyclin have been elevated during experimental acute respiratory failure (ARDS). The present study evaluates the relationship of plasma levels of thromboxane A2 and prostacyclin, measured by radioimmunoassay as the stable metabolites thromboxane B2 (TxB) and prostaglandin 6-K-F1 alpha (PGI) to the incidence of clinical ARDS. Sixty-seven consecutive patients at risk for ARDS were studied prospectively. TxB, PGI, platelet, and leukocyte counts were measured daily for up to 5 days. Of 55 patients without cerebral injury, 25 (45%) developed ARDS, and 30 did not. Of 12 patients with cerebral injury, none developed ARDS. This difference was highly significant (P less than 0.01). TxB was increased and age lower with head injury (P less than 0.05). PGI was significantly lower in ARDS (110 +/- 32 vs 227 +/- 211 pg/ml, P less than 0.05), and mean TxB was unchanged. TxB was increased in age greater than 60 and decreased with prostaglandin inhibitors. ARDS was significantly associated with TxB greater than 70 pg/ml, PGI below the detectable level of 103 pg/ml, TxB/PGI ratio greater than 0.7, and age greater than 60 years. Peak TxB occurred before or simultaneously with onset of ARDS in 68%. Leukocytes were decreased in ARDS (8.6 +/- 4 vs 11.1 +/- 4.4 X 10(3)/mm3) and platelets were unchanged. ARDS was decreased with steroid therapy. Elevated TxB is related to a high incidence of ARDS. Elevated PGI may protect against ARDS. Cerebral injury patients in this study were resistant to ARDS in spite of increased TxB.

6-Ketoprostaglandin F1 alpha↗

Adverse effects of hypothermia in postoperative patients.

The effect of intraoperative and postoperative temperature on morbidity, mortality, and other clinical risk factors was evaluated in 100 consecutive general surgical patients admitted postoperatively to a surgical intensive care unit. Hypothermia (temperature less than 97 degrees F) was present in 77 percent of the patients intraoperatively, in 53 percent at the end of surgery, and in 21 percent at 4 hours. Mortality was increased with patient age greater than 55 years, emergency surgery, operative blood pressure less than 100 mm Hg, operative fluid requirements greater than 1,500 ml/hour, temperature less than 97 degrees F at 2, 4, and 8 hours postoperatively, and presence of postoperative complications. Intraoperative fluid requirements were significantly greater for patients with mortality risk factors. Patients over 55 years of age were more often hypotensive and hypothermic than younger patients, but mortality was increased only for patients less than 55 years of age with a temperature of less than 97 degrees F at 8 hours or an operative blood pressure of less than 100 mm Hg. Mortality after general surgical procedures is increased with operative hypotensive and prolonged postoperative hypothermia. Hypothermic patients with mortality risk factors should be aggressively rewarmed postoperatively.

Female↗

Positive pressure respirations and pneumatic antishock garment application--hemodynamic response.

Pneumatic antishock garment (PASG) application has been recommended for treatment of hypovolemic hypotension and intraperitoneal or retroperitoneal hemorrhage. Often these patients require positive pressure respiration (PPR). This study measured the hemodynamic response of low pressure PASG application, with and without PPR, in normovolemic man and the effects of PASG application on serum lactate. Ten patients after coronary artery bypass surgery were studied with PPR and PASG application (3 to 20 hours post-surgery), and PASG alone (24 to 30 hours post-surgery). PASG pressures of 0,5,10,20, and 0 mm Hg were applied for 10 minutes each after which LAP, PCWP, CVP, mean arterial pressure, heart rate, cardiac index, and serum lactate level were measured. PASG application produced significant elevations in right and left ventricular filling pressures. The left ventricular filling pressure response was significantly less with positive pressure respiration. The CVP and LAP increase did not result in a greater cardiac index. Serum lactate levels rose slightly during PASG application. Low-pressure PASG application results in an 'autotransfusion' effect which is greater without PPR.

Blood Pressure↗

Thromboxane, prostacyclin, and the hemodynamic effects of graded bacteremic shock.

This study investigates the interaction of thromboxane, prostacyclin, and the hemodynamic dysfunction of graded bacteremia. Arterial, venous, and pulmonary artery catheters were inserted into eight adult female pigs under barbiturate anesthesia. After a 60-min control period Aeromonas hydrophila (1.0 X 10(9)/ml) was infused intravenously at 0.2 ml/kg/hr, increasing gradually to 4.0 ml/kg/hr at 4 hr. Hemodynamic measurements, blood gases, and radioimmunoassay of thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI) were performed during the control period, at 10, 20, 30, 45, 60, 75, and 90 min of bacteremia and at 30-min intervals thereafter. During the bacterial infusion, cardiac index (CI), mean arterial pressure (MAP), paO2, pvO2, stroke volume (SV), and left ventricular stroke work (LVSW) decreased significantly, and pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and intrapulmonary shunt (Qs/Qt) increased significantly. TxB was significantly increased at 30 min and remained elevated thereafter. PGI did not rise above control levels until after 240 min of bacterial infusion. TxB cross-correlated most frequently with CI, PVR, SV, paO2, and Qs/Qt, changes in TxB preceding the other variables by 0-60 min. PGI cross-correlated significantly with MAP, LVSW, CI, paO2, and Qs/Qt, changes in PGI preceding MAP, LVSW, and CI by 0-60 min, but following paO2 and Qs/Qt by 30-60 min. TxB is increased early in graded bacteremia and appears related to cardiorespiratory dysfunction. PGI increases late in graded bacteremia, following the onset of respiratory failure, and may mediate the arterial hypotension of septic shock.

6-Ketoprostaglandin F1 alpha↗

The incidence of metastases after multimodal therapy for cancer of the head and neck.

Combined therapeutic regimens integrating chemotherapy, radiation therapy, and surgery are reported to be effective in treating advanced squamous cell carcinomas of the head and neck. The current study evaluates 58 consecutive patients with advanced (T4, N3) head and neck cancers. Forty patients (multimodal group) were treated with 2 courses of chemotherapy (cisplatin 2 mg/kg; methotrexate 280-560 mg/m2 with leucovorin rescue; bleomycin 30 mu X 3) followed by radiation therapy and surgery. Eighteen patients (combined group) were treated with preoperative radiation therapy followed by surgery. In the multimodal group there were 27 (67.5%) partial responses and nine (22.5%) complete responses, for an overall response rate of 90%. Response rates by site of primary lesion were: oral cavity, 11 of 11; oropharynx, 13 of 17; hypopharynx, 5 of 5; and larynx 7 of 7. Distant metastases (skin, lung, bone, central nervous system [CNS]) appeared in 16 patients (40%) (P less than 0.05 versus combined) at a median time of 8.5 months after diagnosis, 15 in patients having a partial (11) or complete (4) response. Thirteen patients (33%) developed distant metastases within 1 year of diagnosis (P less than 0.05 versus combined). In 11 of these patients, the primary lesion and neck disease were resectable. Two thoracotomies were performed for solitary pulmonary metastases; one was resected for cure. Fifteen patients (38%) underwent curative resection; 11 (73%) were alive at 1 year, and ten (67%) were free of disease. Overall survival was 20 of 40 (50%) at 1 year. In the combined group, there were 14 partial responses (78%) and no complete responses. Early distant metastases appeared in two patients (12.5%), at 2 and 6 months after diagnosis. Seven patients (38%) underwent curative resection; six of seven (86%) were alive at 1 year, four of seven (57%) were disease-free. Six of 16 patients at risk (37.5%) survived 1 year. After combined therapy, six of ten patients (60%) with responses to therapy survived 1 year versus 12 of 20 responders (57%) without distant metastases in the multimodal group. It is concluded that multimodal therapy for advanced head and neck cancer results in a higher response rate than with conventional combined therapy. The incidence of early and postoperative distant metastases was increased after the multimodal regimen. At 1 year there were no differences in survival between the combined and multimodal groups for responders without early metastases. Further observation is needed to determine the net long-term effects of this regimen. A prospective randomized comparison of combined and multimodal therapy for advanced lesions is indicated.

Antineoplastic Combined Chemotherapy Protocols↗

Staphylococcus epidermidis sepsis in surgical patients.

We examined 58 surgical patients with two or more blood cultures positive for Staphylococcus epidermidis to determine factors associated with risk, mortality, and invasive sepsis. Bacterial sepsis was associated with gastrointestinal (GI) operations, total parenteral nutrition, and a regimen of two or more parenteral antibiotics. Mortality was 46% overall and significantly increased with age greater than 50 years, GI operations, other gram-positive sepsis, recurrent sepsis (positive blood culture 24 hours or more after the first blood culture), and the presence of organisms sensitive to three or less antibiotics. Antibiotic therapy appropriate for more than 50% of the S epidermidis organisms cultured from each patient resulted in significant reduction in mortality. Staphylococcus epidermidis should be considered a significant pathogen in critically ill surgical patients. Invasive S epidermidis sepsis can be recognized and requires specific antibiotic therapy.

Adolescent↗

Thromboxane interaction with cardiopulmonary dysfunction in graded bacterial sepsis.

The relationship between plasma levels of thromboxane A2, radioimmunoassayed as thromboxane B2 (TxB), and cardiopulmonary dysfunction in graded bacterial sepsis was investigated. Five adult female pigs under anesthesia were intubated and allowed to breathe room air spontaneously. Femoral arterial, venous, and pulmonary artery catheters were inserted. After a 60-minute control period Aeromonas hydrophila (1.0 X 10(9)/ml) was infused intravenously at 0.2 ml/kg/hr, gradually increasing to 4.0 ml/kg/hr over 4 hours. Arterial and mixed venous blood gases, hemodynamic measurements, and TxB plasma concentrations were obtained during the control period, at 10, 20, 30, 45, and 60 minutes and at 30-minute intervals thereafter. Cardiac index increased significantly from control at 20 minutes, remained above control levels for 1 hour, and then declined to significantly low values at 150 minutes. TxB was increased from control at 20 minutes, rising to four times control at 120 minutes. Mean arterial pressure, pulmonary capillary wedge pressure, left ventricular stroke work, paO2, and pvO2 decreased significantly during the experiment. Pulmonary artery pressure and pulmonary vascular resistance increased significantly. Changes in TxB were significantly cross-correlated with changes in cardiac index, pulmonary vascular resistance, stroke volume, left ventricular stroke work, and paO2. TxB elevations led the cross-correlated variables by 0 to 60 minutes. Pulmonary vascular resistance cross-correlated with mean arterial pressure and cardiac index. TxB is increased early in graded bacterial sepsis. Changes in TxB appear to precede impaired cardiopulmonary function. The data suggest that TxB is involved in the detrimental hemodynamic effects of early septicemia.

Animals↗

Crush syndrome with death following pneumatic antishock garment application.

PASG is commonly employed for the prehospital therapy of traumatic hypovolemic hypotension. Although complications are reportly uncommon, several reports of compartment syndromes after PASG application and the present report of a crush syndrome following PASG application raise serious questions about the currently accepted guidelines for PASG therapy.

Adult↗

Fungal sepsis in surgical patients.

Records of 65 surgical patients with positive fungal blood cultures were reviewed to address risk, overall mortality, and treatment. Negative urine cultures did not rule out sepsis. Staphylococcus epidermidis sepsis was present in 27 (42%) of the patients. In 70% of whom it occurred before or during fungemia. Increased mortality correlated with the use of multiple antibiotics, antibiotic use for prolonged periods, and with associated bacterial sepsis. Stopping antibiotic therapy did not reduce mortality. Amphotericin B reduced mortality in patients with dissemination, indicating that it is the treatment of choice for disseminated fungemia and that antibiotic therapy should not be discontinued when concomitant bacterial sepsis is present.

Adolescent↗

The hemodynamic effect of profound hypercapnia on acute hypoxic respiratory failure.

The effect of profound hypercapnia on acute hypoxic respiratory failure is evaluated. Eight dogs were subjected to oleic acid-induced acute respiratory failure. Four dogs were ventilated normally, and four dogs were made hypercapneic by rebreathing exhaled CO2. In the hypercapneic animals, heart rate and alveolar-arterial oxygen difference were significantly lower than in normocapneic animals, while mixed venous O2 cardiac index, oxygen delivery index, stroke volume index, and left ventricular stroke work were significantly higher. Mean arterial pressure was maintained at preinjury levels. Pulmonary and systemic vascular resistance increased in both experimental groups. There was no significant difference between groups for gravimetric determination of lung water. Cardiopulmonary performance in acute respiratory failure is improved with hypercapnia. This may be related to CO2-induced catecholamine release.

Acute Disease↗

Histologic and hemodynamic effects of prostacyclin and prostaglandin E1 following oleic acid infusion.

The hemodynamic and histologic effects of exogenous prostacyclin (PGI2) and prostaglandin E1 (PGE1) on oleic acid-induced acute respiratory failure were investigated. Adult mongrel dogs infused with oleic acid were treated with saline solution, PGE1, and PGI2. Significantly lowered blood pressure, systemic and pulmonary vascular resistance, and arteriovenous oxygen difference and preservation of preoleic cardiac output were observed in the pGI2 group. Compared with the saline group, only the arteriovenous oxygen difference was improved with PGE1. Light microscopy revealed acute edema and inflammation in the saline- and PGE1-treated lungs. Histologic specimens in the PGI2 group were normal.

Animals↗

The effect of radiofrequency hyperthermia on the Ca755 murine adenocarcinoma.

Radiofrequency (RF) was used to induce hyperthermia in the Ca755 murine adenocarcinoma. Thermal kinetic studies revealed a selective heating of tumors over normal tissues during RF, which occurred in larger but not smaller tumors. Small tumors required a significantly greater RF output than did larger neoplasms for heating to the tumoricidal range of 42 C. Rates of tumor growth were not changed after single RF treatments at 42 C, but tumors receiving three applications of RF were significantly smaller than a control group at 28 days tumor age. RF may be of value in the treatment of large neoplasms by using multiple applications; however, microscopic mitoses may not be affected directly without simultaneously damaging normal tissues in the RF field.

Adenocarcinoma↗