In quest of optimal resuscitation: tissue specific, on to the microcirculation.
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Biomedical subjects
Publications and source records attributed to H Sugerman.
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Despite the effects of hyperinsulinemia and hyperglycemia, 2 factors known to inhibit endogenous glucose production (EGP) in nondiabetic subjects, increased EGP is a consistent feature of type 2 diabetes. Recent studies have suggested that increased glucose-6-phosphatase (G6Pase) and/or decreased glucokinase (GK) may explain the increase in EGP. However, no studies to date have clearly established this relationship in type 2 diabetes. The present studies were designed to determine rates of EGP and the activities of G6Pase and GK in obese patients scheduled for gastric bypass surgery. The study group consisted of 14 obese nondiabetic subjects and 13 patients with type 2 diabetes (BMI 53.7 +/- 2.4 vs. 50.1 +/- 1.6 kg/m2). Rates of EGP were determined after an overnight fast with a 4-h infusion of [6,6]-D-glucose, and they were significantly higher in the type 2 diabetic patients (85.9 +/- 10.0 vs. 137.8 +/- 14.4 mg x m(-2) x min(-1), P < 0.001) despite greater plasma glucose (5.1 +/- 0.1 vs. 12.0 +/- 1.1 mmol/l) and similar insulin concentrations (130.8 +/- 19.8 vs. 112.8 +/- 16.2 pmol/l, NS). Moreover, resistance to insulin-induced suppression of EGP was observed in the patients with type 2 diabetes when insulin concentrations were increased from approximately 120 to 180 pmol/l. Hepatic G6Pase activity determined from freshly isolated microsomes was significantly increased in the type 2 diabetic patients compared with the obese control subjects (0.16 +/- 0.02 vs. 0.09 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.02), whereas levels of GK were decreased (1.20 +/- 0.16 vs. 2.01 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.01). Net flux through G6Pase was significantly increased in type 2 diabetic patients (P < 0.01). We conclude that increased EGP is mediated in part by increased G6Pase flux in type 2 diabetes.
BACKGROUND: To determine the ability of an externally applied continuous negative abdominal pressure device (CNAP) to reverse the effects of elevated intra-abdominal pressure on the central nervous and cardiovascular systems. METHODS: Anesthetized, ventilated swine had catheters placed for measurement of intra-abdominal (IAP), intracranial (ICP), central venous, pulmonary artery, pulmonary artery occlusion, mean arterial, peak inspiratory, inferior vena cava, and femoral vein pressures. After the animals stabilized, baseline measurements were obtained. IAP was increased by incrementally instilling an isosmotic polyethylene glycol solution into the peritoneal cavity until it was 25 mm Hg above baseline. IAP was maintained at 25 mm Hg above baseline for 2 hours. CNAP was then applied for 2 hours. All parameters were remeasured 30 minutes after each increase in IAP, at 2 hours after attaining maximum IAP, and lastly at 2 hours after abdominal decompression. Cardiac index was maintained near baseline by volume expansion. RESULTS: Elevation of IAP to 25 mm Hg above baseline for 2 hours caused increases (p<0.05) in central venous pressure (10.3+/-0.9 to 15.2+/-1.7), inferior vena cava pressure (13.0+/-1.0 to 29.5+/-1.5), femoral vein pressure (13.5+/-0.5 to 33.3+/-1.3), ICP (10.6+/-1.5 to 21.0+/-1.5), and peak inspiratory pressure (18.3+/-0.3 to 34.2+/-1.0). The mean arterial pressure (106.3+/-3.5 to 125.8+/-3.4), pulmonary artery pressure (24.3+/-2.3 to 31.3+/-1.7), and pulmonary artery occlusion pressure rose (12.3+/-0.9 to 17.5+/-3.5), but not significantly. Cardiac index (3.3+/-0.5 to 3.4+/-0.4) remained essentially unchanged. CNAP significantly (p<0.05) decreased IAP (30.7+/-1.3 to 18.2+/-1.3), central venous pressure (15.2+/-1.7 to 12.4+/-2.1), inferior vena cava (29.5+/-1.5 to 19.2+/-1.3), and ICP (21.0+/-1.5 to 16.2+/-1.3). Pulmonary artery occlusion pressure (17.5+/-3.5 to 15.0+/-3.1) and peak inspiratory pressure (34.2+/-1.0 to 29.7+/-1.1) decreased, but not significantly. CONCLUSION: Acutely elevated IAP causes a significant increase in ICP and impaired cardiovascular and pulmonary function. Abdominal decompression remains the standard of care for abdominal compartment syndrome. However, in patients in whom an increased IAP does not require surgical decompression, the results of this study suggest that externally applied CNAP may be of value.
OBJECTIVE: Evaluate the effects of surgically induced weight loss on intra-abdominal pressure at one year, reflected in urinary bladder pressure, central obesity, measured by sagittal abdominal diameter and obesity co-morbidity. DESIGN: Prospective, non-randomized trial. SETTING: University Hospital, Operating Room, In-patient, Outpatient Clinics. SUBJECTS: Gastric bypass in 15 severely obese patients. MEASUREMENTS: Patients underwent pre-operative assessment of weight, body mass index (BMI), co-morbid history, urinary bladder pressure and sagittal abdominal diameter. Patients were reassessed one year after gastric bypass with repeat measurement of weight, bladder pressure, and sagittal abdominal diameter and assessment of co-morbidity. RESULTS: There were significant (P < 0.001) decreases in weight (140+/-8 - 87+/-6 kg), BMI (52+/-3 - 33+/-2 kg/m2), sagittal abdominal diameter (32+/-1 - 20+/-2 cm), urinary bladder pressure (17+/-2 - 10+/-1 cm H2O) and obesity related problems per patient (2.9+/-0.4 - 1+/-0.2) one year after gastric bypass, with 69+/-4% loss of excess weight. CONCLUSIONS: Increased sagittal abdominal diameter is associated with increased intra-abdominal pressure which contributes to obesity related co-morbidity. Weight loss following gastric bypass decreases abdominal pressure, sagittal abdominal diameter and obesity co-morbidity.
OBJECTIVES: To determine relationship of intra-abdominal pressure to central obesity and the comorbidity of obesity. DESIGN: Non-randomized, prospective. SETTING: University hospital, operating room. SUBJECTS: Eighty-four anaesthetized consecutive patients prior to gastric bypass for morbid obesity and five non-obese patients before colectomy for ulcerative colitis. MAIN OUTCOME MEASURES: Weight, body mass index (BMI), co-morbid history, sagittal abdominal diameter, waist:hip (W:H) ratio and urinary bladder pressure, as an estimate of intra-abdominal pressure. RESULTS: Urinary bladder pressure was greater in the obese than the non-obese (18 +/- 0.7 vs. 7 +/- 1.6 cm H2O, P < 0.001), correlated with sagittal abdominal diameter (r = +0.67, P < 0.001) and was greater (P < 0.05) in patients with, than those without, morbidity probably (hypoventilation, gastroesophageal reflux, venous stasis, stress incontinence, incisional hernia) or possibly (hypertension, diabetes) due to increased abdominal pressure. W:H ratio correlated with urinary bladder pressure in men (r = +0.6, P < 0.05) but not women (r = -0.3). CONCLUSIONS: Increased sagittal abdominal diameter was associated with increased intraabdominal pressure which contributed to obesity-related comorbidity. W:H ratio was not a reliable indicator of intra-abdominal pressure for women who often have both peripheral and central obesity. Further studies are needed to evaluate the relationship between intra-abdominal pressure and Type II diabetes and hypertension.
Radionuclide assessment of pulmonary capillary protein leak using [99mTc] human serum albumin (99mTc-HSA) was first reported from our laboratory. In this study we investigated the impact of 1) sampling time post tracer injection, and 2) lung region assignment, on diagnostic accuracy between 2 groups (control n = 20 and ARDS n = 20). Each patient received 370 MBq 99mTc-HSA i.v. and was imaged for 45 min. The slope index (SI) [change in lung: heart activity ratio/min] was calculated from 11 computer assigned lung regions for intervals of 5-15 (early [E]) and 15-45 (late [L]) min. The diagnostic accuracy of E vs L SI calculations for the 11 regions was evaluated by stepwise logistic regression. E SI data and L SI data from the lower 1/3 of the lung did not achieve significance for inclusion in the discriminant model (P less than 0.05). In the nine remaining regions L SI was significant. Optimal discrimination was achieved from L SI data obtained from a region confined to the lateral half of the mid 3rd of the lung field (sensitivity 81%, specificity 85%, accuracy 83%). The results confirm that: 1) a late (15-45 min) sampling period and 2) proper region assignment are necessary to maximize accuracy of this technique.
This study was done to better define the immunoregulatory mechanisms in the human intestinal lamina propria (LP). Peripheral blood (PB) and LP cells were obtained from patients having intestinal resections. CD4+ and CD8+ cell subsets were isolated using hybridoma antibodies in a panning technique. Graded numbers of LP and PB CD8+ cells were added to cultures of autologous fresh B cells plus CD4+ cells plus pokeweed mitogen. After 10 days incubation in vitro, the supernatants were collected, and IgM and IgA synthesis was measured by isotype-specific sandwich ELISA. Both PB and LP CD8+ cells suppressed IgM and IgA synthesis by indicator cultures consisting of 5 X 10(4) B cells plus 5 X 10(4) CD4+ cells to a comparable extent. However, when these same CD8+ cells were added to indicator cultures of 5 X 10(4) B cells plus 10(5) CD4+ cells, PB CD8+ cells still suppressed, but LP CD8+ cells enhanced IgM and IgA synthesis. LP but not PB CD8+ cells also augmented IgM and IgA synthesis in cultures with suboptimal immunoglobulin synthesis. Despite these results, LP CD8+ cells were not able to provide help for B cell immunoglobulin synthesis when these two cell types were cultured together with pokeweed mitogen. The mechanism of immunoglobulin augmentation by LP CD8+ cells appeared to involve antagonism of a CD4+ rather than CD8+ suppressor cells. We conclude that functional heterogeneity is more evident within the LP CD8+ subset, with both suppressor and contra-suppressor activities demonstrable, with the latter representing a major activity in LP but not in PB CD8+ cells.
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