PubMed Health⌕ Search

Biomedical subjects

G J Slotman

Publications and source records attributed to G J Slotman.

At least 55 records · Page 3Linked to original sources
PubMed1992

The effects of prostaglandin E1 on non-pulmonary organ function during clinical acute respiratory failure. The Prostaglandin E1 Study Group.

The effects of prostaglandin E1 (PGE1) on non-pulmonary vital organs in critically ill patients are not well defined. This study evaluated the role of exogenous PGE1 in systemic homeostasis during the adult respiratory distress syndrome (ARDS). Indicators of end-organ function were analyzed retrospectively in 146 septic or post-trauma patients with ARDS who received PGE1 (30/ng/kg/min) or placebo IV for up to 7 days in a randomized, double-blind clinical trial. Hemodynamic variables and serum levels of creatinine, bilirubin, and SGOT, platelet count, and changes in the white blood cell count were measured daily. Our results indicate that mean arterial pressure, pulmonary artery pressure, and systemic and pulmonary vascular resistance indices were significantly lower in the PGE1 group versus the placebo-treated group. Cardiac index, stroke index, and oxygen delivery index were significantly increased in the PGE1 group. Serum bilirubin and SGOT were decreased significantly among PGE1-treated patients compared with placebo-treated patients, while the white blood cell count increased more significantly from baseline values with PGE1 treatment. Intergroup differences in platelet count and serum creatinine levels were not statistically significant. The results indicate that PGE1 improves cardiovascular performance, hepatic function, and leukocyte availability during clinical ARDS. Prostaglandin E1 did not affect platelet counts and renal function in this study.

Acute Disease↗
PubMed1989

Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group.

The sepsis syndrome represents a systemic response to infection and is defined as hypothermia (temperature less than 96 degrees F) or hyperthermia (greater than 101 degrees F), tachycardia (greater than 90 beat/min), tachypnea (greater than 20 breath/min), clinical evidence of an infection site and with at least one end-organ demonstrating inadequate perfusion or dysfunction expressed as poor or altered cerebral function, hypoxemia (PaO2 less than 75 torr), elevated plasma lactate, or oliguria (urine output less than 30 ml/h or 0.5 ml/kg body weight.h without corrective therapy). One hundred ninety-one patients with the sepsis syndrome were evaluated prospectively and comprised the placebo group of a multicenter trial of methylprednisolone in sepsis syndrome and septic shock. Forty-five percent of the patients were found to be bacteremic. Thirty-six percent of the patients were in septic shock (sepsis syndrome plus a systolic BP less than 90 mm Hg or a decrease from baseline in systolic BP greater than 40 mm Hg) on study entry. An additional 23% of the patients developed shock after admission with 70% doing so within 24 h of study entry. Shock reversal occurred with a 73% frequency. Twenty-five percent of the patients developed the adult respiratory distress syndrome (ARDS). Mortality for the patients with sepsis syndrome who did not develop shock was 13%. Mortality for the groups of patients with shock on admission and shock postadmission was 27.5% and 43.2%, respectively. Forty-seven percent of the bacteremic patients developed shock after study admission compared to 29.6% of the nonbacteremic patients (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature↗
PubMed1989

Decompression after gastric surgery. Gastrostomy versus nasogastric tube.

The efficacy and associated morbidity and mortality of gastrostomy (G) versus nasogastric (NG) tube decompression after gastric surgery were analyzed in a review of 100 patients. Age, sex, and risk factors were homogeneously distributed between the two groups, while perforated ulcers and emergency operations were more common in the G group. A gastrostomy did not completely eliminate the need for NG tube decompression in the G group. Postoperative morbidity was similar in the two groups, with the exception of an increased incidence of atelectasis in the elective NG group and increased mortality in the emergency G group. There was also a significant increase in length and cost of hospitalization in the emergency G group compared with emergency NG patients. Gastrostomy does not appear to offer any significant advantage over nasogastric decompression after gastric surgery and should be limited to special cases.

Adult↗
PubMed1988

Plasma thromboxane A2 and prostacyclin concentrations in squamous cell carcinoma of the head and neck.

Circulating prostaglandins, including thromboxane A2 and prostacyclin, have been implicated as possible facilitative agents in the growth and dissemination of squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the relationship of plasma concentrations of these compounds to tumor stage and the effect of surgical resection on plasma prostaglandin levels. Blood samples were obtained from 40 patients with head and neck cancer. Ten treated patients were clinically disease-free (NED), and 30 patients with active disease were previously untreated at the time of this study. Plasma concentrations of thromboxane A2 and prostacyclin were measured by radioimmunoassay of their stable metabolites thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI). Platelet aggregation was performed with normal donor platelets (PRP) and normal control or patient plasma (PPP). TxB and TxB/PGI ratios were increased in T1N0M0 patients, compared with NED and with T4N0M0 primary lesions versus all other groups. With lymphatic and hematogenous metastases, TxB and TxB/PGI ratios fell to NED levels. ADP-induced platelet aggregation was significantly increased in head and neck cancer patients, compared with normal controls, and with T4N0M0 lesions, compared with NED. There were no significant differences in PGI levels. TxB, PGI, TxB/PGI, and platelet aggregometry did not change significantly with curative surgery. TxB and TxB/PGI interactions are involved in head and neck cancer. Changes in TxB and TxB/PGI may be related to increased platelet aggregation.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Ketoconazole: a thromboxane synthetase and 5-lipoxygenase inhibitor with antimetastatic activity in B16-F10 melanoma.

Arachidonic acid metabolites have been implicated in the development of hematogenous tumor metastases. The purpose of this study was to determine the antimetastatic potential of ketoconazole, a thromboxane synthetase and 5-lipoxygenase inhibitor. One hundred seventy-four C57 black male mice were randomized to receive either placebo or 0.0057 mg/g of ketoconazole. Drug and placebo were delivered once daily by intraperitoneal injection beginning 24 hr prior to tumor injection and continuing until sacrifice. All animals were injected subcutaneously in the flank with 5 x 10(6) B16-F10 melanoma cells. Animals were sacrificed at 3 weeks (n = 60), 4 weeks (n = 84), and 5 weeks (n = 30). Metastases were assessed by circumferential inspection of the lungs of all animals at autopsy. Differences in survival and primary tumor mass between study groups were not statistically significant. Pulmonary metastases were present in 37/174 animals. Twenty-nine of the mice with metastases were in the placebo groups, and 8 were in the ketoconazole groups. The incidence of metastases was significantly reduced in the ketoconazole-treated mice compared to placebo both within each group and overall, P was less than 0.05 and 0.001, respectively. This effect was not mediated through changes in local tumor growth.

Animals↗
PubMed1988

Effect of ischemic skin flap elevation on tissue and plasma thromboxane A2 and prostacyclin production: modification by thromboxane synthetase inhibition.

The circulating prostaglandins have been implicated as mediators of microcirculatory derangements in skin and skin-muscle flaps. The study described here investigated the roles of thromboxane A2 and prostacyclin, measured as thromboxane B2 (TxB2) and prostaglandin 6-keto-F1a (PGF1a), in ischemic skin flaps, and the effects of thromboxane synthetase inhibition on flap blood flow and survival. A canine ventral island flap model was used to measure the appearance of TxB2 and PGF1a in the central arterial and venous plasma, and in the tissue and venous effluent of acutely raised flaps; with and without pretreatment with the specific thromboxane A2 synthetase inhibitor UK38485. Prostaglandin levels change significantly during flap elevation, and can be modified beneficially by thromboxane A2 synthetase inhibition, causing dramatic increases in flap blood flow and survival, as predicted by intravital dye penetration. The results presented in this article suggest that the manipulation of these compounds may provide a method of producing a pharmacological delay phenomenon and perhaps even allow effective intervention in the failing flap.

Animals↗
PubMed1988

Ketoconazole prevents acute respiratory failure in critically ill surgical patients.

Effective prophylaxis against acute respiratory failure (ARDS) has not been established. This study investigated whether or not ketoconazole could prevent ARDS in critically ill surgical patients. Seventy-one Surgical Intensive Care Unit (SICU) patients without liver dysfunction received either ketoconazole (n = 35), 200 mg daily via the gastrointestinal tract, or placebo (n = 36), for 21 days or until discharge from the SICU, in a prospective, randomized, double-blind study. Patients were monitored clinically for signs of ARDS, defined as all the following: intrapulmonary shunt greater than 15%, a PaO2/FIO2 ratio less than 150, normal central venous, pulmonary capillary wedge, or left atrial pressure, no other cause of hypoxemia, and a consistent chest X-ray. Thirteen patients (18%) developed ARDS with significantly increased mortality versus non-ARDS patients (69% vs. 29%). The incidence of ARDS was decreased among ketoconazole patients compared to placebo (6% vs. 31%; p less than 0.01), as was median SICU stay (7.0 days vs. 15.5 days; p less than 0.05), and median SICU cost (+5,600. vs. +12,400.; p less than 0.05). Mortality is increased with ARDS after trauma and surgery. We conclude that ketoconazole prevents ARDS, shortens SICU stay, and lowers hospital costs.

Adolescent↗
PubMed1987

A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.

Adult↗
PubMed1987

Ketoconazole prevents Candida sepsis in critically ill surgical patients.

We conducted a prospective, randomized, double-blind, placebo-controlled study to determine whether or not ketoconazole could prevent yeast colonization or invasion in critically ill adult surgical patients. Fifty-seven patients in a surgical intensive care unit (SICU) with three or more clinical risk factors for Candida infection were randomized to receive ketoconazole, 200 mg via the gastrointestinal tract daily (27 patients), or placebo (30 patients). Patients with hepatic dysfunction were excluded. The study was continued for 21 days or until one week after discharge from the SICU, whichever was longer. Stool cultures were obtained every three days and other cultures as indicated clinically. Patients were observed for yeast colonization (sputum, urine, stool, or wound) and invasion (fungemia or deep tissue focus). The incidence of Candida colonization was significantly lower in the ketoconazole group than the placebo group. Invasive yeast sepsis developed in five (17%) of the placebo-treated patients and in no patient in the ketoconazole group, a significant difference. Length of stay in the SICU was significantly lower in the ketoconazole group, as were the basic SICU patient charges. Sixty percent of the patients with invasive fungal sepsis died.

Adult↗
PubMed1987

Interaction of thromboxane A2 and tissue pathology during graded bacteremia.

The purpose of this study was to determine whether or not thromboxane A2 (TXA2) was necessary or sufficient for the development of end-organ pathology during graded bacteremia. Pulmonary artery catheters were placed in 21 adult male pigs under pentobarbital anesthesia and breathing room air. After a control period, animals were studied in four groups: Group 1, anesthesia only; Group 2, infusion of 1 X 10(9) ml Aeromonas hydrophila which was gradually increased from 0.2 ml/kg/hr to 4.0 ml/kg/hr over 4 hours; Group 3, pretreatment with SQ 29,548 (TXA2 antagonist) then Aeromonas h. infusion; Group 4, infusion of U46619 (TXA2 agonist) to pulmonary artery pressures measured in Group 2. Animals were sacrificed after 4 hours and the lungs, liver, spleen, kidneys, and heart were examined under light microscopy by a pathologist unaware of study groups. The results indicated that physiologic thromboxane A2 agonist (Group 4) was sufficient alone to cause pulmonary inflammation. Thromboxane A2 was neither necessary nor sufficient for significant renal, hepatic, pulmonary, or splenic pathology to occur in graded bacteremia, manifested in similar microanatomic abnormalities in these organs in Groups 2 and 3 and in Groups 1 and 4. Pulmonary leukocyte infiltration was significantly increased in Group 3 compared to all other groups, suggesting that TXA2 impairs inflammatory responses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Early methylprednisolone treatment for septic syndrome and the adult respiratory distress syndrome.

From November 1, 1982 through December 31, 1985, there were 19 centers and 382 patients that evaluated the effect of methylprednisolone sodium succinate (MPSS) on the septic syndrome. Seventeen of these centers enrolled 304 patients in a prospective, randomized, double-blind, placebo-controlled study to determine if early treatment with MPSS would decrease the incidence of severity of the adult respiratory distress syndrome (ARDS) in patients at risk of ARDS from sepsis. To ensure early institution of the MPSS or placebo therapy (PLA), patients with the presumptive diagnosis of sepsis were identified. That diagnosis was based on the presence of fever or hypothermia (temperature greater than 38.3 degrees C or less than 35.5 degrees C, rectal), tachypnea (greater than 20 bpm), tachycardia (greater than 90 bpm) and the presence of one of the following indices of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels or oliguria. The treatment, either MPSS 30 mg/kg or PLA, was given in four 20-minute infusions six hours apart and was initiated within two hours of the presumptive diagnosis of sepsis. The development and reversal of the adult respiratory distress syndrome (ARDS) was followed and resulted in data on 304 of the 382 randomized patients. A trend toward increased incidence of ARDS was seen in the MPSS group 50/152 (32 percent) compared to the placebo group 38/152(25 percent) p = 0.10. Significantly fewer MPSS patients reversed their ARDS 15/50 (31 percent) compared to placebo 23/38 (61 percent) p = 0.005. The 14-day mortality in patients with ARDS treated with MPSS was 26/50 (52 percent) compared to placebo 8/22 (22 percent) p = 0.004. We conclude that early treatment of septic syndrome with MPSS does not prevent the development of ARDS. Additionally, MPSS treatment impedes the reversal of ARDS and increases the mortality rate in patients with ARDS.

Adolescent↗
PubMed1986

Prostaglandin and complement interaction in clinical acute respiratory failure.

This study investigated the interaction of plasma levels of circulating prostaglandins and activated complement in clinical acute respiratory failure (ARDS). Fifty patients at risk for ARDS were followed up for up to ten days. Arterial blood gases and plasma levels of complement components C3a and C5a, thromboxane B2 (TxB), and prostaglandin 6-keto-F1 alpha (PGI) and granulocyte aggregation (GA) were measured daily. Seventeen patients (34%) developed ARDS, with mortality of 41% vs 23% for patients without ARDS. Compared with patients without ARDS, the ARDS group had significantly increased plasma C3a (1,130 +/- 750 vs 636 +/- 368 ng/mL) and granulocyte aggregation (48 +/- 10 vs 17 +/- 4 percentage of the maximum light transmission [% max T]). Plasma C5a, TxB, or PGI did not change significantly with or without ARDS. No measured variable was significantly associated with mortality. Regression analysis revealed significant correlations between GA, TxB, PGI, and arterial oxygenation. Plasma C3a and GA are increased in ARDS, suggesting systemic complement activation. A complex series of interactions between the prostaglandins, complement, and GA appears to be involved in ARDS.

Acute Disease↗
PubMed1986

Leukocyte aggregation response to quantitative plasma levels of C3a and C5a.

Granulocyte aggregation (GA) response has previously been described as a sensitive assay for complement activation in sepsis. Complement component C5a has been implicated as the plasma factor responsible for GA. The quantitative interaction of complement components C3a and C5a with GA, however, is not clearly defined. This study evaluates the relationship of GA responses to plasma levels of C5a and C3a in zymosan-activated plasma (ZAP). The C3a and C5a levels were measured by radioimmunoassay in serial dilutions of ZAP. Granulocyte aggregation responses of normal human leukocytes were determined for each ZAP dilution. The C5a levels in a 1:16 dilution of ZAP were higher than in normal plasma (22 +/- 7 vs 9 +/- 3 ng/mL), as were GA responses (24 +/- 1 vs 11 +/- 2 percentage of maximum light transmission). The C3a levels in a 1:8 dilution of ZAP are elevated above those of normal plasma (656 +/- 167 vs 411 +/- 29 ng/mL). Correlation coefficients were .9809 for C3a vs GA, .9788 for C5a vs G, and .9860 for C3a vs C5a. Complement components C3a and C5a are involved in GA in vitro. Granulocyte aggregometry can detect low levels of activated complement in ZAP but may not be specific for C5a. The relative contribution of C3a and C5a to observed GA is not clear from the data.

Cell Aggregation↗
PubMed1986

Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension.

Activated complement, thromboxane A2, prostacyclin, and activated granulocytes have been implicated in hemodynamic dysfunction after trauma, in sepsis, and in hypovolemic and septic shock. This study evaluated the interaction of plasma concentrations of complement components C3a and C5a, thromboxane B2 (TxB), prostaglandin 6-keto-F1 alpha (PGI), and granulocyte aggregation in clinical sepsis and hypotension. Forty-eight critically ill patients were followed clinically for as long as 10 days. Plasma C3a, C5a, TxB, and PGI were measured daily by the radioimmunoassay method. Granulocyte aggregation, the percentage of maximum aggregation of zymosan-activated plasma standard curves, was performed with patient plasma and normal human leukocytes. Patients were studied in four groups: group I, nonseptic, normotensive; group II, hypovolemic shock, group III, normotensive severe sepsis; and group IV, septic shock. Plasma from 12 normal adults was the control value. PGI, TxB, C3a, C5a, and granulocyte aggregation in patients were greater than that in the control subjects. Granulocyte aggregation was increased in groups III and IV versus groups I and II. C3a was increased in group IV versus groups II and III. C5a and TxB did not vary between groups. PGI was greatly increased in group IV compared with groups I through III. C3a and C5a decreased in nonsurvivors. PaO2/FiO2 ratios correlated directly with PGI and inversely with C3a and TxB/PGI. Plasma PGI and C3a are increased in septic shock. C3a and TxB/PGI imbalances are involved in hypovolemic and septic shock.

Adolescent↗
PubMed1986

Microbial filtrates activate granulocytes without complement or prostaglandins.

UNLABELLED: Cardiorespiratory dysfunction in sepsis may be mediated by circulating complement, activated leukocytes, prostaglandins, or by a direct effect of endotoxin. The purposes of this study were to determine if pathogenic microbes produce these substances and to evaluate the direct effects of substances released by micro-organisms on granulocyte aggregation (GA). Escherichia coli, (E. coli), Aeromonas hydrophila (Aeromonas h.), Staphylococcus aureus (S. aureus), and Candida albicans, (Candida a.) were incubated in broth to a concentration of 10(9)/ml. Broth was filtered and analyzed by radioimmunoassay for complement components C3a and C5a, thromboxane B2 (TxB), and prostaglandin 6-keto-F1 alpha (PGI) and by the limulus amebocyte lysate test (LAL) for endotoxin. GA, % of maximum zymosan activated aggregation (% max. T), was performed with broth, microbial filtrates, and endotoxin or normal purified human leukocytes in HBSS. Organisms were incubated in broth (B), broth + 0.0135 mg/ml arachidonic acid (BA), and broth + arachidonic acid + indomethacin (BAI). Broth alone was the control (C). RESULTS: C3a, C5a, TxB, and PGI were not detectable in C broth or in any microbian filtrate. LAL was positive in all filtrates, but negative in C broth. GA responses were significantly greater in E. coli (56 +/- 5% max T) and Aeromonas h. (57% +/- 8% max T) compared to S. aureus (10 +/- 5% max T), Candida a. (14 +/- 8% max T) and C broth (1 +/- 1% max T). GA with purified E. coli endotoxin at concentrations measured in the filtrates was not related to the GA responses the original filtrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗