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Biomedical subjects

M J Girotti

Publications and source records attributed to M J Girotti.

51 records · Page 3Linked to original sources

Comparison of regional pulmonary perfusion in lobar pneumonia during high frequency and conventional mechanical ventilation in sheep.

We compared the effects of high frequency jet ventilation (HFV), conventional ventilation (CMV), and spontaneous breathing (SB) on regional pulmonary blood flows (QLLL), standard cardiopulmonary measurements and the serum levels of the first generation metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane A2 (TxB2) in established left lower lobe pseudomonas aeruginosa pneumonia in 11 sheep. Gram negative pneumonia resulted in significant increases in alveolar-arterial oxygen gradients [(A-a)DO2] and pulmonary shunt fractions (Qs/Qt), as well as a significant decrease in QLLL during SB. Significant differences in standard haemodynamics, (A-a)DO2, Qs/Qt, and QLLL were not observed when HFV was compared to CMV. However, serum levels of 6-keto-PGF1 alpha were elevated when the animals underwent HFV. We conclude that HFV is a safe and efficient method of oxygenation and ventilation in unilobar gram negative pneumonia and also results in a significant increase in the serum levels of 6-keto-PGF1 alpha when compared to CMV in sheep. The exact significance of the latter finding is the subject of current investigation.

6-Ketoprostaglandin F1 alpha↗

Experimental gram-negative pneumonia produces a hyperdynamic septic profile.

General anesthesia (GA) and extensive surgery undertaken to reproduce a hyperdynamic septic shock syndrome (HSSS) may confound the observed effects of pure HSSS. A large animal model of HSSS without GA or surgery was created in sheep following production of a Pseudomonas pneumonia by direct bronchoscopic instillation into a dependent lobe using only light ketamine anesthesia. Cardiac output rose significantly (5.05 to 6.32 L/min) while SVR [1,421.4 to 1,000.5 dynes X s X cm(-5)] and mean BP (92.5 to 82.0 mmHg) fell in the septic animals. Systemic infection was confirmed by blood culture. This model reliably produces hyperdynamic sepsis without the confounding effects of GA or extensive surgery.

Animals↗

Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity.

The effects of antibiotics and other commonly used medications on the human polymorphonuclear neutrophil leukocytes' (PMNs) nicotinamide-adenine dinucleotide phosphate-reduced (NADPH) oxidase activity have been investigated in vitro. Five antibiotics (penicillin G sodium, cefamandole nafate, metronidazole hydrochloride, clindamycin phosphate, and tobramycin sulfate, and a triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate) and two sedatives (morphine sulfate and diazepam) were incubated with normal human PMNs at therapeutic, infratherapeutic, and supratherapeutic drug levels. The superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome C in the PMNs was studied after stimulation with formyl-methionyl-leucine-phenylalanine. Tobramycin sulfate and the triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate significantly reduced the NADPH oxidase activity at all dosages studied. Clindamycin phosphate, morphine sulfate, and diazepam also showed significant reduction at therapeutic and supratherapeutic concentrations. Penicillin G sodium, cefamandole nafate, and metronidazole hydrochloride did not cause a decrease in enzyme activity at any levels tested. We conclude that NADPH oxidase activity can be adversely affected by the circulating levels of common antibiotics and sedatives.

Adult↗

Factors predicting discharge from intensive care: a Canadian experience.

This study prospectively analyzed 481 admissions to a multidisciplinary intensive care unit in order to determine factors which may prove helpful in predicting outcome from an intensive care admission. Severity of illness was assessed by the admission acute physiology score and daily therapeutic intervention scoring system. Age, sex, diagnosis upon admission, nature of the admission (medical vs. surgical, emergency vs. elective) were also studied. Our results indicate that the admission acute physiology score during the first three days of the admission and thereafter, the daily therapeutic intervention scores from the previous day are the most reliable predictors of outcome from intensive care. Age was related to outcome only when it was associated with emergency and medical type admissions. A linear logistic regression analysis was used to construct a model predicting mortality within the intensive care unit based on acute physiology score and nature of the admission.

Age Factors↗

Reducing the costs of ICU admission in Canada without diagnosis-related or case-mix groupings.

A prospective analysis of the cost of intensive care was carried out on 67 admissions to a multidisciplinary ICU. Admissions were grouped and investigated according to various criteria such as admitting diagnosis, admission status (elective vs emergency), severity of illness and outcome. Total ICU admission costs, total per diem ICU costs and per diem costs divided into fixed and variable cost items for the patient groups are reported. Lower total and per diem ICU charges were observed for elective surgical patients, patients with lower severity of illness as assessed by the Therapeutic Intervention Scoring system and survivors. Emergency admissions were more expensive than elective admissions when compared for total ICU admission costs. Length of stay was a significant factor in overall ICU costs. Within the variable cost items, the diagnostic laboratory was the single most costly item per day. As a result of this analysis, the authors propose several suggestions for reducing ICU costs independent of case-mix or diagnosis-related groupings of ICU patients.

Age Factors↗

PMN superoxide radical production following a metabolic-endocrine simulation of trauma.

Serious infections following major trauma remain inexplicably high. Metabolic and endocrine changes after injury have been suggested as being responsible for many of the documented defects in the polymorphonucleocyte (PMN). The in vitro bactericidal activity of normal human PMNs has been examined in this laboratory by assaying the activity of the PMN membrane bound enzyme NADPH oxidase and hence O2- production of the PMN in a metabolic/endocrine milieu designed to simulate moderately severe trauma. This was accomplished by incubating the PMN with physiological and trauma serum concentrations of insulin, glucose, cortisol, epinephrine, and glucagon. The results indicate that the O2- production of the PMN is significantly enhanced in this environment. It would appear that exogenous glucose alone was responsible for this enhanced O2- production.

Adult↗

Simultaneous use of membrane oxygenation and high-frequency jet ventilation in acute pulmonary failure.

A 16-yr-old female suffering acute, rapidly progressive combined respiratory and cardiac failure that was unresponsive to conventional volume-cycled ventilation, was stabilized with the simultaneous short-term use of veno-venous membrane oxygenation and high-frequency jet ventilation. Percutaneously introduced cannulas afforded rapid vascular access for membrane oxygenation, minimal wound problems during the perfusion, and easy decannulation. This is the first reported combined use of high-frequency jet ventilation and extracorporeal membrane oxygenation, and the first reported percutaneous initiation of veno-venous bypass. The patient remained alive and well 4 months after therapy.

Acute Disease↗

Effect on cardiopulmonary changes of gram-negative endotoxemia in sheep after type-specific, cross-reactive, and nonspecific immune stimulation.

The purpose of this study was to examine the effects of prior nonspecific immune stimulation (BCG), cross-reactive immunization (E coli J5 0111 whole cells [J5 WC], and core glycolipid [J5 CGL]), and type-specific immunization (Serratia marcescens core glycolipid [SM CGL]) on the cardiopulmonary variables and white blood cell counts of awake, monitored sheep following IV Serratia marcescens endotoxin. Comparison of cardiac output, pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, alveolar-arterial oxygen gradients, and total white blood cells lead us to conclude that type-specific immunization (SM CGL) most effectively ameliorates the changes of gram-negative endotoxemia contrasted to nonimmunization. Core glycolipid cross-reactive (J5 CGL) immunization was somewhat more effective than whole-cell cross-reactive (J5 WC) immunization in this regard. Nonspecific immune stimulation (BCG) was able only to significantly decrease the changes in pulmonary vascular resistance compared to nonimmunization.

Animals↗

The pneumatic antishock garment: use in experimental acute cardiac tamponade.

Acute cardiac tamponade was created in a large animal model in an effort to investigate the hemodynamic and oxygen transport variables during the inflation of the pneumatic antishock garment (PASG) to two different pressures (60 and 80 mm Hg). Inflation of PASG to either pressure under these conditions had no significant effects on filing pressures to the right or left heart, cardiac index, arterial blood gases, oxygen delivery, indexed pulmonary, and systemic vascular resistances. We conclude in this animal model of acute cardiac tamponade that no beneficial or harmful effects were demonstrated during the application and inflation of the pneumatic antishock garment to 60 or 80 mm Hg.

Animals↗

Delayed intestinal perforation after nonpenetrating abdominal trauma.

The incidence of hollow-organ injury has increased steadily since the use of seat-belts was introduced. It has become apparent that the clinical manifestations of intestinal injury may be delayed considerably. Delayed perforations can pose a diagnostic challenge to the attending surgeon. The authors report four patients who suffered delayed intestinal perforation 6 or more days after sustaining nonpenetrating abdominal trauma in motor vehicle accidents while wearing passive seat-belt restraints. All patients had low severity of injury (scores ranging from 4 to 13) but had persistent vague abdominal pain before perforation occurred. Three of the four patients suffered spinal trauma as their major initial injury. Such patients appear to be at higher risk for delayed perforation and should be monitored carefully.

Abdominal Injuries↗

Effects of immunization on cardiopulmonary alterations of gram-negative endotoxemia.

We studied the effects of an infusion of Serratia marcescens endotoxin on hemodynamic function, white blood cells, platelets, and the plasma levels of thromboxane B2 (TXB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in awake monitored sheep. The animals were immunized using the core glycolipid (CGL) fraction of Escherichia coli J5 0111. An additional group of animals was studied after passive transfer of immune serum from the actively immunized CGL animals. Active immunization with CGL was effective in preventing the hematologic and hemodynamic changes as well as the elevations in TXB2 and 6-keto-PGF1 alpha seen during gram-negative endotoxemia. Passive immunization also reduced some of the deleterious effects of endotoxin infusion but was less effective than active immunization. This study demonstrates the potential of cross-specific immunization to protect against the cardiopulmonary alterations caused by gram-negative endotoxemia.

6-Ketoprostaglandin F1 alpha↗

Amphojeloma: antacid impaction in a critically ill patient.

Patients in the intensive care unit seldom have mechanical small-bowel obstruction, and obstruction due to medication bezoars is even less common. A 65-year-old woman, in the intensive care unit because of septic shock and acute renal failure, had a small-bowel obstruction due to Amphojel concretions. Obstruction from such a cause may be prevented by including non-constipating antacids, stool softeners or sorbitol. Aggressive use of H2-antagonists to prevent gastrointestinal bleeding in septic patients will reduce the need for orally administered antacids. When obstruction occurs due to antacid concretions, it may be relieved by passing a long intestinal tube, by giving enemas for colonic obstruction or by operation.

Acute Kidney Injury↗