Search PubMed⌕ Search

Biomedical subjects

H J Sugerman

Publications and source records attributed to H J Sugerman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Release of endothelin in relation to tumor necrosis factor-alpha in porcine Pseudomonas aeruginosa-induced septic shock.

Septic shock is characterized by surges of tumor necrosis factor-alpha (TNF-alpha) along with myocardial dysfunction and systemic hypotension. TNF-alpha promotes the release of immunoreactive endothelin (ET). Because TNF-alpha is elevated in septic shock, we hypothesized that elevated levels of endothelin can contribute to cardiac dysfunction and hypotension. We infused live Pseudomonas aeruginosa into anesthetized, hemodynamically monitored young swine and measured ET and TNF-alpha. Septic swine developed systemic arterial hypotension and had significantly elevated TNF-alpha (4.15 +/- .41 U/ml at 1 h versus .40 +/- .13 U/ml at time zero) compared to control animals. ET levels were significantly elevated at 4 h (52.38 +/- 12.88 pg/ml vs. 10.45 +/- 1.82 pg/ml at time zero) and correlated negatively with the decline in cardiac output. We then passively immunized swine using anti TNF-alpha prior to the induction of sepsis to examine if TNF played a central role in the release ET. The anti TNF-alpha effectively removed circulating TNF-alpha bioactivity in septic animals. Anti-TNF-alpha-treated animals did not develop significant systemic arterial hypotension and had significant attenuation in endothelin (19.01 +/- 4.18 pg/ml at 4 h compared to 52.38 +/- 12.88 pg/ml in septic animals at 4 h) which correlated with preservation of cardiac output. TNF-alpha may cause cardiac dysfunction in sepsis syndrome through increased release of ET.

Animals↗
PubMed1994

Death in the operating room: an analysis of a multi-center experience.

To characterize causes of death in the operating room (OR) following major trauma, a retrospective review of admissions to eight academic trauma centers was conducted to define the etiology of death and challenges for improvement in outcome. Five hundred thirty seven OR deaths of 72,151 admissions were reviewed for mechanism of injury, physiologic findings, resuscitation, patterns of injury, surgical procedures, cause of death, and preventability. Blunt injuries accounted for 61% of all injuries, gunshot wounds (GSW) accounted for 74% of penetrating injuries. Sixty two percent of all patients arrived in shock. Average blood pressure (BP) was 52 mm Hg at the scene and 60 mm Hg on admission, with the period of shock > 10 minutes in 74%. Only 56% were resuscitated to a BP > 90 mm Hg before surgery. Average time to the OR was 30.1 minutes and mean best postresuscitation pH was 7.18. Mean best OR temperature was 32.2 degrees C. Recurrent injury patterns judged as the primary cause of patient death included head/neck injury (16.4%), chest injury (27.4%), and abdominal injury (53.4%). Actual cause of death was bleeding (82%), cerebral herniation (14.5%), and air emboli (2.2%). A different strategy for improved outcome was identified in 54 patients with the following conclusions: (1) delayed transfer to the OR remains a problem with significant BP deterioration during delay, particularly following interfacility transfer; (2) staged injury isolation and repair to allow better resuscitation and warming may lead to improved results; (3) combined thoraco-abdominal injuries, particularly with thoracic aortic disruption, often require a different sequence of management; (4) aggressive evaluation of retroperitoneal hematomas is essential; (5) OR management of severe liver injuries remains a technical challenge with better endpoints for packing needed; and (6) resuscitative thoracotomy applied to OR patients in extremis from exsanguination offers little.

Adult↗
PubMed1993

Role of the neutrophil in adult respiratory distress syndrome.

Adult respiratory distress syndrome (ARDS) remains a significant cause of morbidity and mortality in surgical practice. Despite the continued advance of surgical technique and therapy, the mainstay of treatment of ARDS remains supportive. In the past decade cytokines have been found to be primary chemical mediators of the host response to inflammatory disease. The polymorphonuclear leucocyte has also emerged as a possible cellular mediator of the end-organ damage that characterizes these inflammatory processes. The role of the neutrophil as the primary cellular mediator of alveolar capillary membrane injury in ARDS remains controversial. This article reviews the relevant current literature and considers the implications of the prevailing evidence on future management of this syndrome.

Cell Movement↗
PubMed1993

Gallbladder mucin, arachidonic acid, and bile lipids in patients who develop gallstones during weight reduction.

BACKGROUND: Arachidonic acid (AA) and hydrophobic bile salts (BS) stimulate gallbladder mucin (GBM) secretion, which is thought to be an essential step in gallstone pathogenesis. The present study was performed to evaluate the relationship between AA, BS, and GBM in patients who develop gallstones following weight reduction. METHODS: Eleven patients who underwent gastric bypass, developed symptomatic gallstones, and then underwent cholecystectomy were evaluated. Gallbladder bile was obtained for analysis during each procedure. Matched patients who did not develop gallstones following gastric bypass served as controls. RESULTS: GBM increased in every patient who developed stones (mean increase: 5000%). The largest increase was observed soon after gastric bypass, and this declined curvilinearly with time. Gallbladder bile cholesterol was initially elevated but then rapidly declined before increasing back to pregastric bypass levels after weight loss was complete. No significant changes in phosphatidylcholine molecular species (including AA) or BS composition were observed following weight reduction. Concentrations of cholesterol, phospholipids, and changes in [AA] over time were each a linear function of [BS]. No relationship between GBM and any of these bile constituents was apparent. CONCLUSIONS: These observations strongly suggest that increases in GBM, which occur with gallstone formation in humans, are not the result of alterations in biliary AA or BS composition.

Adult↗
PubMed1993

Combined ibuprofen and monoclonal antibody to tumor necrosis factor-alpha attenuate hemodynamic dysfunction and sepsis-induced acute lung injury.

A number of key mediators are implicated in the pathophysiology of sepsis. In previous studies of a septic porcine model, ibuprofen pretreatment prevented the early but not the late rise in pulmonary vascular resistance index (PVRI) and the early but not the late fall in arterial PO2 (PaO2), whereas monoclonal antibody to tumor necrosis factor alpha (anti-TNF alpha) prevented the late but not the early rise in PVRI and the late but not the early fall in PaO2. This study examined the impact of pretreatment with combined ibuprofen and anti-TNF-alpha on the course of sepsis and acute lung injury (ALI) in pigs. Three groups were studied for 5 hours. Groups I (n = 9) and II (n = 5) received a 1-hour infusion of Pseudomonas aeruginosa. Group II received ibuprofen (12.5 mg/kg) and anti-TNF-alpha (5 mg/kg) before P. aeruginosa, and a further bolus of ibuprofen at 120 minutes. Group III (n = 11) received sterile saline. Group I demonstrated a significant (p < 0.05) rise in plasma TNF-alpha that was abolished in group II. The SVRI in group II did not change significantly from baseline through the study and the SVRI rose sharply in group I following onset of the infusion of P. aeruginosa, as did PVRI. There was no significant change in PVRI from baseline in group II, except for the final 60 minutes; PVRI in group II was significantly less than in group I throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pharmacologic reduction in tumor necrosis factor activity of pulmonary alveolar macrophages.

Tumor necrosis factor-alpha (TNF), an inflammatory cytokine released by macrophages, may be a mediator of lung injury during septicemia. We previously reported that the cyclooxygenase inhibitor ibuprofen and histamine receptor antagonists cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) attenuate lung injury and reduce circulating TNF surges during porcine sepsis. Since pulmonary alveolar macrophages (PAM) may participate in early sepsis by producing TNF, we hypothesized that the TNF activity of PAM is reduced by ibuprofen, cimetidine, and diphenhydramine. To test this, we examined changes in PAM-derived TNF bioactivity and cell viability of freshly isolated porcine PAM during exposure to bacterial endotoxin (LPS), ibuprofen, cimetidine, and diphenhydramine. The TNF activity (% L929 cytotoxicity of PAM conditioned medium) was elevated in LPS-stimulated PAM cultures (15 to 25% increase at 1 to 6 h and 40 to 43% increase at 6 to 48 h, compared with non-LPS-stimulated cultures), and ibuprofen (150 micrograms/ml) added with LPS decreased the TNF activity for 24 h (20 to 28% reduction at 1 to 24 h). Ibuprofen added 1 h after LPS was less effective in reducing the PAM-derived TNF activity (20 to 22% reduction at 2 to 6 h). Cimetidine (112 micrograms/ml) reduced the TNF activity of LPS-stimulated PAM cultures during the first 4 h of LPS exposure (15 to 24% decrease at 1 to 4 h). Diphenhydramine (150 micrograms/ml) attenuated the PAM-derived TNF activity but also decreased viability of PAM, indicating a toxic effect of this agent on PAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation.

Tumor necrosis factor (TNF alpha), both by direct action and by trafficking cells of the immune system, is implicated in cardiopulmonary derangements and PMN-mediated microvascular injury associated with gram-negative sepsis. We examined the effects of pretreatment with a monoclonal antibody to TNF alpha on PMN function, hemodynamic derangements, and alveolar capillary membrane damage in a septic porcine model. Anti-TNF alpha profoundly improved hemodynamic consequences in this model. Reduction in PMN CD11/18 receptor expression, lung myeloperoxidase activity, and attenuation of peripheral neutropenia (all P < 0.05) indicate that pretreatment significantly reduced lung sequestration of PMNs seen in septic controls. In contrast, PMN oxygen radical (O2-) generation was not significantly different from unprotected septic animals. Despite the presence of circulating PMNs primed for O2- burst, alveolar capillary membrane damage, assessed by bronchoalveolar lavage protein content and arterial PO2 was markedly attenuated in the treatment group (P < 0.05). We conclude that anti-TNF alpha suppresses systemic hemodynamic actions of TNF alpha. Further, it prevents upregulation of PMN adhesion receptors inhibiting PMN/endothelial cell interaction. This prevents formation of a "microenvironment," protected from circulating oxidant scavengers, into which sepsis-activated PMNs release their toxic products. Pretreatment with anti-TNF alpha monoclonal antibody thus affords global protection in porcine Gram-negative sepsis.

Animals↗
PubMed1993

Gallstones in patients with morbid obesity. Relationship to body weight, weight loss and gallbladder bile cholesterol solubility.

Gallstones are common in obesity, and in individuals undergoing weight reduction. However, the relationships between body weight, weight reduction, gallbladder bile composition and gallstone formation are not well understood. The present studies were conducted on a cohort of 230 morbidly obese individuals presenting for bariatric surgery. Mean body weight ranged from 90-235.4 kg (mean: 136.2 kg). Body mass index (BMI) ranged from 35.4-94.7 kg/m2. Thirty-two patients (14%) had undergone prior cholecystectomy and 48 (21%) were found to have gallstones by intraoperative ultrasonography. No significant relationship was observed between gallstone prevalence and body weight. Following bariatric surgery weight loss averaged 1.57 kg/week over six months. Absolute weight loss ranged from 13.6-81.3 kg. Symptomatic gallstones requiring cholecystectomy developed in 15/150 patients (10%) over two years of follow-up. In contrast, ultrasonography detected asymptomatic gallstones in 34/92 patients (37%) six months following bariatric surgery. No relationship existed between the amount of weight lost and gallstone formation. Gallbladder bile cholesterol solubility remained constant throughout the entire weight range present in this population. No significant difference in cholesterol solubility was present between persons presenting for bariatric surgery and patients who developed symptomatic gallstones and underwent cholecystectomy following weight reduction. We conclude that gallstones are common in patients with severe obesity both before and following bariatric surgery. However, weight loss per se does not appear to be the major determinant of gallstone formation in persons who weigh in excess of 100 kg.

Adult↗
PubMed1992

Monoclonal antibody to tumor necrosis factor alpha attenuates cardiopulmonary dysfunction in porcine gram-negative sepsis.

Tumor necrosis factor (TNF) is implicated in the pathophysiology of gram-negative sepsis. This study examined physiologic and biochemical effects of pretreatment with an anti-TNF alpha monoclonal antibody immediately before the onset of sepsis. Three groups of anesthetized ventilated pigs were studied for 300 minutes. Groups 1 (n = 12) and 2 (n = 6) received a 1-hour infusion of live Pseudomonas aeruginosa. Group 2 was pretreated with anti-TNF alpha monoclonal antibody (15 mg/kg). Group 3 (n = 8) received intravenous sterile saline. Group 1 exhibited a significant rise in plasma TNF activity, which was abolished in group 2. Cardiac index was reduced in both groups 1 and 2 in the first hour but recovered in group 2 (3.3 +/- 0.4 l/min per square meter at 300 minutes in group 2 vs 1.3 +/- 0.2 L/min per square meter in group 1). Metabolic acidosis was attenuated (arterial pH, 7.39 +/- 0.01 in group 2 vs 7.16 +/- 0.03 at 300 minutes in group 1). Increased extravascular lung water was also attenuated (5.9 +/- 0.7 in group 2 vs 13.2 +/- 1.5 mL/kg at 300 minutes in group 1). However, pulmonary hypertension and hypoxemia, which are known cyclooxygenase effects, were not affected. In the early phase of the study, plasma thromboxane B2 levels were elevated in both groups 1 and 2. We conclude that anti-TNF alpha monoclonal antibody offered significant protection against the effects of sepsis, but that other mediators may be responsible for the early changes seen in this model.

Animals↗
PubMed1992

Changes in gallbladder bile composition following gallstone formation and weight reduction.

Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18-fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile.

Adult↗
PubMed1992

Obesity and lower urinary tract function in women: effect of surgically induced weight loss.

OBJECTIVE: The subjective and objective effects of massive weight loss on lower urinary tract function in morbidly obese women were examined. STUDY DESIGN: Thirteen subjects underwent a comprehensive evaluation of lower urinary tract function before and 1 year after surgically induced weight loss. RESULTS: We demonstrated significant improvements in lower urinary tract function after weight loss. Of 12 subjects who complained of incontinence before surgery only three complained of incontinence (p = 0.004) and only one requested treatment after weight loss. Objective and subjective resolution of both stress and urge incontinence was documented. Statistically significant changes were seen in measures of vesical pressure, the magnitude of bladder pressure increases with coughing, bladder-to-urethra pressure transmission with cough, urethral axial mobility, number of incontinence episodes, and the need to use absorptive pads. CONCLUSION: Weight reduction is desirable for obese women complaining of urinary incontinence and may obviate the need for further incontinence therapy.

Adult↗
PubMed1992

Gastric bypass for treating severe obesity.

Gastric bypass (RY-GBP) has a very small gastric pouch with a 1-cm diameter Roux-Y gastrojejunostomy. RY-GBP is associated with early satiety and an aversion to sweets secondary to dumping syndrome symptoms and has a significantly better weight loss than various gastroplasty procedures, including the vertical banded gastroplasty. However, it may be associated with vitamin B-12 deficiency and iron deficiency anemia in menstruating females, preventable with prophylactic oral iron and vitamin B-12. With an 80% 5 y follow-up, RY-GBP patients lose two-thirds of their excess weight within 2 y, 60% at 5 y, and greater than 50% at 9 y. The RY-GBP can be beaten by nibbling "junk foods" (potato or corn chips). Conversion to a malabsorptive procedure may cause severe malnutrition and fat-soluble vitamin deficiencies and should be used only for "superobese" patients who fail a standard RY-GBP and have severe comorbidity. RY-GBP is the most effective procedure for morbid obesity, especially in patients addicted to "sweets."

Gastric Bypass↗
PubMed1992

Long-term effects of gastric surgery for treating respiratory insufficiency of obesity.

The Pickwickian syndrome can be divided into two primary breathing disorders, which can affect patients alone or in combination: sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Between 1980 and 1990, 126 patients with respiratory insufficiency underwent gastric surgery for morbid obesity, 12.5% of the entire series. These patients weighed more (164 +/- 36 vs 135 +/- 25 kg, P less than 0.0001) and were more often men (62% vs 14%, P less than 0.001) than those without pulmonary dysfunction. Sixteen had OHS alone, 65 had SAS alone, and 45 had both. Of those with OHS, 38 have been followed for 5.8 +/- 2.4 y since surgery and 29 are currently asymptomatic. In the 12 patients in whom arterial blood gases were available greater than 5 y since surgery, the PaO2 increased from 54 +/- 10 to 68 +/- 20 mm Hg (P less than 0.0001) and PaCO2 fell from 53 +/- 9 to 47 +/- 11 mm Hg (P = 0.05). Of the 110 patients with SAS, 57 were available for follow-up an average of 4.5 +/- 2.3 y since surgery and 38 were completely asymptomatic, 15 had mild SAS, and 4 had both SAS and OHS. In 40 patients with pre- and post-weight reduction sleep polysomnograms, the sleep apnea index fell from 64 +/- 39 to 26 +/- 26 (P less than 0.0001). Although respiratory insufficiency of obesity patients had a higher operative mortality than did patients without pulmonary dysfunction (2.4% vs 0.2% after gastric bypass), weight loss was associated with significant improvements in sleep apnea, arterial blood gases, pulmonary hypertension, left ventricular dysfunction, lung volumes, and polycythemia.

Adult↗
PubMed1992

Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome.

OBJECTIVE: To determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure. Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients. DESIGN: Prospective study. SETTING: University hospital ICUs. PATIENTS: Thirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: All patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera. Lung-to-heart ratio of tracer was calculated and expressed as the slope index. Increase in slope index indicated increased pulmonary albumin flux. Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was greater than 30 mm Hg. Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups. A subgroup of patients in the septic group had a normal slope index. Septic patients with an increased slope index had a significantly (p less than .01) longer duration of mechanical ventilation (36 +/- 5 vs. 7 +/- 1 days), spent longer in the ICU (67 +/- 9 vs. 11 +/- 1 days), and had a longer hospital stay (113 +/- 20 vs. 35 +/- 5 days) than septic patients with a normal slope index. CONCLUSIONS: Gamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP less than 30 mm Hg from patients with sepsis-induced ARDS. Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (greater than 2 SD above control mean) had a markedly increased morbidity.

Adult↗
PubMed1992

The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries.

The evaluation and management of patients with minor head injury (MHI: history of loss of consciousness or posttraumatic amnesia and a GCS score greater than 12) remain controversial. Recommendations vary from routine admission without computed tomographic (CT) scanning to mandatory CT scanning and admission to CT scanning without admission for selected patients. Previous reports examining this issue have included patients with associated non-CNS injuries who confound the interpretation of the data and affect outcome. We hypothesized that patients with MHI and no other reason for admission with normal neurologic examinations and normal CT scans would have a negligible risk of neurologic deterioration requiring surgical intervention. To validate this hypothesis we studied 2766 patients with an isolated MHI admitted to seven trauma centers between January 1, 1988, and December 31, 1991. There were 1898 male patients and 868 female patients; injury was blunt in 99%. A neurologic examination and a CT scan were performed on 2166 patients; 933 patients had normal neurologic examinations and normal CT scans and none required craniotomy; 1170 patients had normal CT scans and none required craniotomy; 2112 patients had normal neurologic examinations and 59 required craniotomy. The sensitivity of the CT scan was 100%, with positive predictive value of 10%, negative predictive value of 100%, and specificity of 51%. The use of CT alone as a diagnostic modality would have saved 3924 hospital days, including 814 ICU days, and $1,509,012 in hospital charges. Based on these data, we believe that CT scanning is essential in the management of patients with MHI and that if the neurologic examination is normal and the scan is negative patients can be safely discharged from the emergency room.

Adolescent↗