Biomedical subjects

J V Sitzmann

Publications and source records attributed to J V Sitzmann.

At least 55 records · Page 3Linked to original sources

PubMed1997

TNM staging of pancreatic carcinoma using helical CT.

OBJECTIVE: The purpose of this study was to determine the accuracy of helical CT scanning in predicting the stage of carcinoma of the exocrine pancreas using TNM staging guidelines and in predicting resectability of carcinoma of the exocrine pancreas. MATERIALS AND METHODS: Twenty-six patients with proven adenocarcinoma of the pancreas underwent uniphasic or biphasic helical CT scanning. Two observers unaware of the patient's surgical stage evaluated the CT examinations using the TNM system (with specific assessment and description of disease sites). In addition, the two observers rated confidence of nonresectability using a 5-point scale (ranging from 1, definitely resectable, to 5, definitely not resectable). Observer results and preoperative interpretations were compared with surgical findings. RESULTS: Nineteen of 26 patients had nonresectable disease. The combined observer scores showed correct determination of T stage in 77% of patients, of N stage in 58%, and of M stage in 79%. The overall accuracy in determining lack of resectability was 96% and 84% for the two observers. All errors in determining resectable versus nonresectable disease occurred when the observer was not maximally confident of his or her diagnosis. CONCLUSION: Helical CT is an effective screening technique for assessing T and M stages of pancreatic carcinoma. However, helical CT is poor at detecting regional lymph node involvement. In patients with equivocal T-stage findings (such as questionable venous involvement), other studies such as endoscopic sonography may be of value.

Adenocarcinoma↗

PubMed1996

Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells.

Two important mediators of endothelium-dependent regulation of vascular smooth muscle tone and proliferation are nitric oxide (NO) and endothelin (ET-1). An imbalance between NO and ET-1 may contribute to the alterations in vascular tone characteristic of cardiovascular disease. The objective of this study was to determine whether NO regulates ET receptors in cultured rat superior mesenteric artery vascular smooth muscle cells (RVSMC). Chronic treatment of quiescent RVSMC with any one of three chemically dissimilar NO-generating drugs, S-nitroso-N-acetyl penicillamine (SNAP), sodium nitroprusside (SNP), and isosorbide dinitrate (ISDN) produced a significant dose- and time-dependent increase in the number of ET-A receptors, while concomitantly increasing the affinity of ET-1 for this receptor. This effect was mimicked by both 8-bromo-cGMP and 8-bromo-cAMP. The requirement of both protein and RNA synthesis and activation of a cAMP-dependent protein kinase (A-kinase) was demonstrated following inhibition of this regulation by cycloheximide, actinomycin D and KT5720 (a specific A-kinase inhibitor), respectively. In addition, the cytokine interleukin 1 beta (IL-1 beta) which induced NOS activity with subsequent NO synthesis in vascular smooth muscle, also caused a similar upregulation of ET receptors. This effect was attenuated in the presence of the specific NOS inhibitor, L-NAME. To assess the possible functional consequences of this NO-mediated upregulation, the effect of SNAP pretreatment on isolated vessel reactivity was determined. In both superior mesenteric artery and thoracic aorta rings, SNAP pretreatment caused a significant increase in the maximal force of contraction to ET-1. Collectively, these data suggest that NO regulates ET-A receptors in vitro through a cGMP-dependent mechanism via activation of the cAMP-dependent protein kinase. We conclude that a similar interaction between NO and ET-1 may be operational in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

Simple radiographic evaluation of ileoanal pouch volume.

PURPOSE: Total colectomy and mucosal protectomy with ileal reservoir and anal pull-through is used in the treatment of ulcerative colitis or familial polyposis, with one complication being frequent bowel movements. A simple radiographic test to predict frequency of bowel movements and measure spasticity was evaluated. METHODS: Fourteen patients underwent evaluation after ileal reservoir and anal pull-through J-pouch construction. Barium sulfate suspension was instilled into the pouch via the anus in the standing position until reflux flowed into the small intestine proximal to the pouch and patients felt the urge to defecate. Total volume infused (VOLtot), volume to reflux (VOLrflx), and volume voided (VOLvoid) were measured. RESULTS: VOLvoid and the "voiding efficiency" (VOLvoid/VOLtot) correlated significantly with stool frequency (R=-0.744, P<0.002 and R=-0.754, P<0.002, respectively). Time from operation was correlated with VOLvoid and stool frequency (R=-0.723, P<0.003 and RO.573, P<0.032, respectively). CONCLUSIONS: The addition of quantitative measurements to this radiographic test gives useful information about pouch performance. Furthermore, the data imply that spasticity, as measured by voiding quantum and efficiency, rather than actual pouch volume is a major determinant of bowel movement frequency.

Adult↗

PubMed1996

Pharmacokinetics of regional angiotensin-II: a novel biologic response modifier.

BACKGROUND: The splanchnic vasoconstrictor angiotensin-II (A-II) has been shown to redistribute blood flow to hepatoma during systemic infusions. The hepatoma tumor derives all blood flow from the hepatic artery, whereas the normal liver has a dual blood supply from both the portal vein and the hepatic artery. We hypothesized that the pharmacokinetics of regional intrahepatic arterial A-II infusion could favorably distribute blood flow to the tumor while preserving portal flow to normal liver. METHODS: ACI rats had 10(6) cultured H4IIE cells inoculated into the liver 10-14 days before study. Both systemic and splanchnic hemodynamics were measured by the radio-labeled microsphere technique during intrahepatic arterial or intravenous infusion of angiotensin-II or normal saline. The tumor-to-normal liver hepatic artery blood flow ratio was calculated. RESULTS: Regional A-II produced a proportionately less systemic effect than did intravenous infusion. The tumor vasoconstrictive response to A-II was minimal, and the tumor-to-normal blood flow ratio was greater with intrahepatic arterial or intravenous A-II infusion than with normal saline. Cardiac output and portal vein flow were decreased dramatically during intravenous, but not during intrahepatic, arterial A-II. CONCLUSION: Intrahepatic arterial A-II exhibits saturation kinetics with a system effect observed only after hepatic receptor saturation. Furthermore, the pharmacokinetics of intrahepatic arterial versus intravenous A-II indicate that intrahepatic arterial A-II will preferentially redistribute arterial blood flow to the tumor while synchronously preserving portal blood flow to the normal liver.

Angiotensin II↗

PubMed1996

Regulation of atrial natriuretic factor receptors in portal hypertensive rabbits.

BACKGROUND/AIMS: Portal hypertension is characterized by a marked splanchnic hyperemia due to a reduction in mesenteric vascular resistance. Possible mediators of this decreased resistance include an increased amount of and/or responsiveness to vasodilatory substances. Previous studies have demonstrated an enhanced hypotensive effect of exogenous atrial natriuretic factor in portal hypertension. We hypothesized that changes in the atrial natriuretic factor hormone receptor system may contribute to this response and hence underlie the marked hyperemia of portal hypertension. METHODS: We used a portal-vein-ligated rabbit model of portal hypertension to study the integrity of the atrial natriuretic factor receptor system within the hyperemic vasculature. RESULTS: There was no significant difference in the serum concentrations of sodium, potassium, atrial natriuretic factor, ANG-II, cGMP, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. Superior mesenteric artery, thoracic aorta and portal vein atrial natriuretic factor receptor number and affinity were determined using [125I]-rANF99-126 binding analysis and affinity cross-linking studies. Receptor classification using specific atrial natriuretic factor-C receptor ligands, along with affinity cross-linking studies revealed two receptor subtypes present on these vessels. There was a significant decrease in the number of atrial natriuretic factor receptors in the portal vein and a significant increase in the superior mesenteric artery in portal hypertension without any significant change in affinity. Thoracic aortic atrial natriuretic factor receptors were increased with a concurrent decrease in affinity in portal hypertension. There was a concomitant increase in tissue cGMP levels within the superior mesenteric artery and thoracic aorta of portal hypertensive animals but not the portal vein. CONCLUSION: These data suggest the increased number of functional atrial natriuretic factor receptors may in part contribute to the hyperdynamic splanchnic circulation peculiar to portal hypertension.

Animals↗

PubMed1996

Increased endothelial nitric oxide synthase activity in the hyperemic vessels of portal hypertensive rats.

BACKGROUND/AIM: Portal hypertension is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. Mediators of this hyperemia include nitric oxide. This is based on several reports indicating a marked splanchnic hyporesponsiveness in portal hypertension to vasoconstrictor stimuli both in vitro and in vivo, and a subsequent reversal using specific inhibitors of nitric oxide synthase. The objective of this study was to determine firstly whether the functional activity and/or expression of nitric oxide synthase is altered in portal hypertensive vasculature and secondly which isoenzyme form was responsible for the preferential response to nitric oxide blockade in these animals. METHODS: We compared nitric oxide synthase functional activity in the hyperemic vasculature of sham and portal hypertensive rats (following partial portal vein ligation). Nitric oxide synthase activities were determined by measuring the conversion of L-arginine to citrulline using ion-exchange chromatography and the amount of immunodetectable nitric oxide synthase in sham and portal hypertensive vessels was determined by Western blot. RESULTS: Ca(2+)-dependent nitric oxide synthase activity was significantly elevated (p < 0.05) in portal hypertensive particulate fractions from the superior mesenteric artery, thoracic aorta and portal vein. Vascular tissue cGMP levels and plasma nitrite levels were both significantly elevated in portal hypertension. Immunodetection with specific antisera raised against the inducible nitric oxide synthase demonstrated a lack of induction within the hyperemic vasculature. Immunodetection with antisera against endothelial nitric oxide synthase showed a significant increase in portal hypertensive portal vein only. These results demonstrate enhanced calcium-dependent nitric oxide synthase activity in portal hypertension hyperemic vessels concurrent with elevated tissue cGMP levels. CONCLUSION: We conclude that enhanced endothelial nitric oxide synthesis may in part contribute to the hyperdynamic circulation of portal hypertension.

Animals↗

PubMed1996

Decreased angiotensin II receptors mediate decreased vascular response in hepatocellular cancer.

OBJECTIVE: The authors' objective was to determine the origin of the diminished pressor responsiveness of angiotensin II infusion in hepatoma by evaluating angiotensin II receptor status in normal liver, hepatoma tumor, and cultured hepatocytes and H4IIE cells. SUMMARY BACKGROUND DATA: Hepatocellular cancer is a highly vascular tumor, where the neovasculature is unique in that it arises only from the hepatic arterial circulation, whereas normal liver has both hepatic arterial and portal venous blood supply. The tumor neovasculature is also characterized by an abnormal vascular reactivity to vasoconstrictors, including the response to angiotensin II. The altered response of tumor vasculature to angiotensin II offers a potential therapeutic opportunity for modulation of tumor blood flow. However, the origin of the decreased vascular response is unknown. METHODS: The authors evaluated the hepatic vascular response to angiotensin II infusion by determining hepatic arterial blood flow to normal liver and to tumor by means of radioactive microspheres. The angiotensin II receptor status in the normal liver, hepatoma tumor, and cultured hepatocytes and H4IIE cells was determined br radioligand binding analysis and in cryostat sections derived from normal liver and hepatoma tumor by means of in situ binding analysis with biotinylated angiotensin II. RESULTS: Angiotensin II infusion decreased the hepatic arterial flow to normal liver and increased hepatoma to liver flow ratio. The number of angiotensin II receptors in normal liver was significantly higher than that in hepatoma (239 +/- 20 fmol/mg protein in normal liver vs. 162 +/- 15 fmol/mg protein in hepatoma) without a change in the affinity (4.4 +/- 0.8 nM in normal liver vs. 4.7 +/- 1.2 nM in hepatoma). H4IIE cells and primary hepatocytes had low receptor density. In situ binding analysis revealed that angiotensin II receptors were mainly on the smooth muscle cells of the neovasculature. CONCLUSIONS: The data suggests that the diminished vascular response to angiotensin II hepatoma may relate a loss of angiotensin II receptor on tumor neovasculature.

Angiotensin II↗

PubMed1996

Portal-phase contrast-enhanced helical CT for the detection of malignant hepatic tumors: sensitivity based on comparison with intraoperative and pathologic findings.

OBJECTIVE: The purpose of this study was to determine the sensitivity of portal-phase IV contrast-enhanced helical CT in detecting malignant hepatic tumors using a lesion-by-lesion comparison with surgical and pathologic findings. MATERIALS AND METHODS: Preoperative portal-phase contrast-enhanced helical CT studies in 21 patients (13 men, eight women) with malignant neoplasms of the liver (12 patients with primary hepatic tumors, nine patients with metastases) were reviewed retrospectively by three radiologists with the knowledge that hepatic malignancies were present in each case. Helical CT findings were compared with intraoperative findings by palpation (21 patients), sonography (15 patients), and the results of pathologic examination of resected specimens (10 patients) in a lesion-by-lesion manner. Sixty-four malignant nodules were identified in resected specimens or at surgery by palpation or intraoperative sonography. For each nodule identified by surgical or pathologic means, CT findings were reviewed for the presence of a lesion of similar size and location. RESULTS: The readers identified 52 of 64 nodules on helical CT scans for an overall sensitivity of 81%. Sixteen of 21 primary tumors (76%) and 36 of 43 metastatic tumors (84%) were identified on CT scans. The sensitivity was 91% for nodules greater than 1 cm (42 of 46) and 56% for nodules 1 cm or less (10 of 18). False-positive findings occurred in 4% of lesions seen on helical CT scans. CONCLUSION: Our results show that portal-phase contrast-enhanced helical CT is extremely sensitive (91%) for detecting malignant hepatic tumors greater than 1 cm, is relatively insensitive (56%) for tumors less than 1 cm, and has a low false-positive rate. These results compare favorably with published results for CT during arterial portography, the current gold standard for liver tumor detection, suggesting that portal-phase IV contrast-enhanced helical CT is an excellent noninvasive preoperative study prior to hepatic resection or cryosurgery.

Adult↗

PubMed1996

Hepatic tumors treated by cryosurgery: normal CT appearance.

OBJECTIVE: An understanding of the normal appearance of hepatic tumors treated with cryosurgery is essential for accurately distinguishing normal postoperative changes from potential complications such as hepatic abscess or infarct, which may necessitate further interventions. The purpose of this study was to characterize the normal spectrum of CT findings after cryoablation of hepatic tumors. SUBJECTS AND METHODS: The CT scans of 14 patients who had undergone hepatic cryoablation 4-16 days (mean, 7 days) before scanning were reviewed by three radiologists. None of these patients had postprocedural complications that necessitated intervention (e.g. abscess, infarct, or hemorrhage). Indications for cryoablation included primary hepatic tumors in four patients and hepatic metastases in 10 patients. CT findings were correlated with surgical findings in a lesion-by-lesion manner to ensure that only cryolesions were included in the analysis. RESULTS: Twenty-eight cryolesions from 3 to 11 cm maximum diameter (mean, 7 cm) were detected on CT scans. All cryolesions were primarily hypodense and extended to the liver capsule. Ten (36%) of 28 lesions contained air, and 26 (93%) of 28 lesions contained hemorrhage. Thirteen (54%) of 24 lesions evaluated with i.v. contrast material showed peripheral enhancement. Cryolesions were primarily wedge shaped (54%), round (29%), or teardrop shaped (21%). One iatrogenic portosystemic shunt was detected. Other associated findings included subcapsular hemorrhage (29%), perihepatic fluid collections (43%), right-sided pleural effusion (93%), left-sided pleural effusion (64%), atelectasis of one or both lungs (93%), and ascites (7%). CONCLUSION: The postoperative CT appearance of the liver in patients who underwent hepatic cryoablation without complications mimics that seen in the liver of patients with hepatic abscesses or infarcts. The CT appearance of the liver in patients undergoing cryosurgery needs to be carefully analyzed to avoid confusing normal findings related to the procedure with those related to procedural complications, it may be impossible to differentiate hepatic complications from normal postoperative changes on the basis of CT findings in many of these patients.

Cryosurgery↗

PubMed1995

Nitric oxide regulates angiotensin II receptors in vascular smooth muscle cells.

The objective of this study was to determine whether an enhanced generation of nitric oxide (NO) causes regulation of angiotensin II receptors in vitro using rat vascular smooth muscle cells in culture. Chronic treatment of cells with a series of NO-generating drugs, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate for 18h dose and time-dependently decreased [125I]-angiotensin II binding to cells without any significant change in affinity. Induction of nitric oxide synthase following lipopolysaccharide (10 and 100 ng/ml) treatment of cells for 18 h increased basal nitric oxide synthase activity with a concomitant increase of nitrite and cyclic cGMP levels in the conditioned media. LPS treatment significantly (P < 0.05) decreased [125I]-angiotensin II binding to these cells, an effect that was significantly (P < 0.05) attenuated in the presence of NG-nitro-L-arginine methyl ester. In contrast, treatment of cells with atrial natriuretic factor, dibutyryl cGMP, 8-bromo-cGMP, NaNO2 or NaNO3 failed to significantly alter the affinity or number of [125I]-angiotensin II binding sites. These results suggest that NO regulates angiotensin II receptors in vitro through a cGMP-independent mechanism.

Amino Acid Oxidoreductases↗

PubMed1995

Perfused transcapillary smooth muscle and endothelial cell co-culture--a novel in vitro model.

As most in vitro endothelial cell (EC)-vascular smooth muscle cell (SMC) co-culture studies have been performed utilizing static culture conditions, none have successfully mimicked the physical environment of these cells in vivo. EC covering the inner surface of blood vessels are continuously exposed to a hemodynamically imposed mechanical stress resulting from the flow of blood, while SMC are affected by pressure, a flow-related force acting perpendicular to the surface. We have developed a perfused transcapillary co-culture system that permits the chronic exposure of EC and SMC to physiological shear stresses and pressures. SMC and EC co-cultures were successfully established and maintained in long-term culture (7 wk) on an enclosed perfused bundle of semipermeable polypropylene capillaries. By altering flow rate and/or viscosity, shear stresses of 0.07-20 dyn/cm2 can be readily achieved in this system. Electron microscopic analysis revealed that SMC formed multilayers around the outside of the capillaries, whereas EC, subjected to 3 dyn/cm2 shear stress, formed an intact closely adherent monolayer lining the capillary lumen. EC and SMC exhibited characteristic ultrastructural and gross morphology. EC were separated from SMC by the capillary wall (pore size 0.5 microns, width 150 microM) and while no direct cell-cell contact was evident some cells were seen to migrate into the capillary wall. Both EC and SMC are exposed to the same culture medium, allowing the interaction of substances released in both directions. Yet separate populations of cells are maintained and can be individually harvested for further analysis. This co-culture system that mimics the architecture and physical environment of the vessel wall should have many potential applications in vascular biology.

Animals↗

PubMed1995

Role of cirrhosis in the hemodynamic response to hemorrhage in portal hypertension.

BACKGROUND: We studied hemodynamic alterations in normal and three models of portal hypertension at rest, after hemorrhage, and after resuscitation to determine the role of hepatic dysfunction in the splanchnic vascular response to hemorrhage in portal hypertension. METHODS: One noncirrhotic and two cirrhotic models of portal hypertension were produced in rabbits: partial prehepatic portal vein ligation, common bile duct ligation, and carbon tetrachloride-induced cirrhosis. Animals were subjected to isovolemic hemorrhage followed by reinfusion of shed blood. Portal, central, and aortic pressures, superior mesenteric artery blood flow, and portosystemic shunt were measured. RESULTS: Histologic examination showed parenchymal damage was absent in normal and portal vein ligation, severe in common bile duct ligation, and moderate in carbon tetrachloride-induced cirrhosis. All portal hypertensive animals exhibited diminished splanchnic vasoconstrictive response to hemorrhage compared with normal. The carbon tetrachloride cirrhosis group had severe cirrhotic changes, minimal portosystemic shunt, and mildly diminished constrictive response. In contrast, the portal vein ligation and common bile duct ligation animals had larger portosystemic shunts, markedly diminished constrictive response, and less severe parenchymal damage. A direct correlation existed between magnitude of rise in portal venous pressure or degree of portosystemic shunt and the fall in mesenteric resistance or diminution of vasoconstrictive response to hemorrhage. CONCLUSIONS: We concluded that the abnormal splanchnic vascular response in portal hypertension is relatively independent of the degree of hepatic parenchymal injury, but it is related to the degree of portal hypertension and possibly to splanchnic hyperemia.

Animals↗

PubMed1995

Rectal squamous mucosectomy and ileal anal pull-through procedures: single surgeon experience in 105 patients.

BACKGROUND: The ileal anal pull-through procedure has become the most frequently used cointinence sparing procedure for patients with ulcerative colitis or familial polyposis. Areas of controversy concern the use of temporary ileostomies, and the extent of the rectal mucosectomy. The current report presents a single surgeon's experience with mucosectomy to the perianal skin (squamous mucosectomy), with ileal J-pouch reservoir construction and temporary ileostomy. METHODS: We reviewed the records of 105 consecutive patients undergoing this procedure by a single surgeon during a 5-year period. One hundred percent follow-up was achieved. RESULTS: There was 100% gross fecal continence, with 5% of patients expressing rare day time leakage, and 28% having intermittent nocturnal leakage. There were no instances of pelvic sepsis, and no pouches have been removed. The diverting ileostomy was associated with 6% morbidity. CONCLUSIONS: We conclude that the rectal mucosectomy can be safely extended to the levels of perianal skin with no loss in continence or function. We recommend that this be adopted as the standard for this procedure to ensure complete eradication of the underlying pathologic condition.

Adult↗

PubMed1995

The catecholamine, cortisol, and hemodynamic responses to mild perioperative hypothermia. A randomized clinical trial.

BACKGROUND: Unintended hypothermia occurs frequently during surgery and may have adverse effects on the cardiovascular system. Although the mechanisms responsible for the cardiovascular manifestations of hypothermia are unclear, it is possible that they are sympathetically mediated. In this prospective study, relationships between body temperature, the neuroendocrine response, and hemodynamic changes in the perioperative period were examined. METHODS: Seventy-four elderly patients, undergoing abdominal, thoracic, or lower extremity vascular surgical procedures, were randomly assigned to either "routine care" (n = 37) or "forced-air warming" (n = 37) groups. Throughout the intraoperative and early postoperative periods, the routine care group received standard thermal care, and the forced-air warming group received forced-air skin-surface warming. Core temperature, forearm minus fingertip skin-surface temperature gradient, and plasma concentrations of epinephrine, norepinephrine, and cortisol were measured throughout the perioperative period, and the two groups were compared. In addition, heart rate and arterial blood pressure were compared between groups. RESULTS: The routine care and forced-air warming groups did not differ with regard to age, sex, type of surgical procedures, anesthetic techniques, or postoperative analgesia. Mean core temperature was lower in the routine care group on admission to the postanesthetic care unit (routine care, 35.3 +/- 0.1 degree C; forced-air warming, 36.7 +/- 0.1 degree C; P = 0.0001) and remained lower during the early postoperative period. Forearm minus fingertip skin-surface temperature gradient (an index of peripheral vasoconstriction) was greater in the routine care group in the early postoperative period. The mean norepinephrine concentration (pcg/ml) was greater in the routine care group immediately after surgery (480 +/- 70 vs. 330 +/- 30, P = 0.02) and at 60 min (530 +/- 50 vs. 340 +/- 30, P = 0.002) and 180 min (500 +/- 80 vs. 320 +/- 30, P = 0.004) postoperatively. Mean epinephrine concentrations were not significantly different between groups. Mean cortisol concentrations were increased in both groups during the early postoperative period (P < 0.01), but the differences between groups were not significant. Systolic, mean, and diastolic arterial blood pressures were significantly higher in the routine care group. CONCLUSIONS: Compared with patients in the forced-air warming group, patients receiving routine thermal care had lower core temperatures, a greater degree of peripheral vasoconstriction, higher norepinephrine concentrations, and higher arterial blood pressures in the early postoperative period. These findings suggest a possible mechanism for hypothermia-related cardiovascular morbidity in the perioperative period.

Aged↗

PubMed1995

Multivariate determinants of early postoperative oxygen consumption in elderly patients. Effects of shivering, body temperature, and gender.

BACKGROUND: Previous investigators have proposed that postoperative shivering may be poorly tolerated by patients with cardiopulmonary disease because of the associated significant increase in total-body oxygen consumption. However, the often-quoted 300-400% increase in oxygen consumption with shivering was derived from relatively few studies performed in a small number of younger persons specifically selected on the basis of clinically recognizable shivering. We hypothesized that the average elderly postoperative patient has a shivering response that is associated with a relatively small increase in total-body oxygen consumption. METHODS: One hundred eleven elderly patients (age > 60 yr) undergoing surgery were studied to assess the determinants of shivering and total-body oxygen consumption in the early postoperative period. Anesthetic technique, postoperative analgesia, and thermal management were controlled by protocol. The clinical variables associated with shivering and increased total-body oxygen consumption were determined by univariate and multivariate analyses. RESULTS: Mean total-body oxygen consumption in shivering patients was 38% greater than in nonshivering patients. Regardless of whether data from shivering patients were included in the analysis, oxygen consumption was directly proportional to mean body temperature. Despite similar core temperatures, men had a greater incidence of clinically recognizable shivering and greater total-body oxygen consumption than did women. CONCLUSIONS: The metabolic demands associated with postoperative shivering in elderly patients are less than those reported previously in younger persons. These findings suggest that if hypothermia predisposes to cardiovascular complications in the postoperative period, these complications are not likely to be mediated by shivering and increased metabolism.

Aged↗

PubMed1995

Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients.

OBJECTIVE: This single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. METHODS: Two hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. RESULTS: The overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections; n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, < 800 mL intraoperative blood loss, < 2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection. CONCLUSIONS: The survival of patients with pancreatic adenocarcinoma treated by pancreaticoduodenectomy is improving. Aspects of tumor biology, such as DNA content, tumor diameter, nodal status and margin status, are the strongest predictors of outcome.

Actuarial Analysis↗

PubMed1995

Enhanced nitric oxide synthase activity in portal hypertensive rabbits.

Portal hypertension (PHT) is characterized by splanchnic hyperemia caused by a reduction in mesenteric vascular resistance. Mediators of this hyperemia include nitric oxide (NO). This is based on several reports indicating a marked splanchnic hyporesponsiveness in PHT to vaso-constrictor stimuli, both in vitro and in vivo, and a subsequent reversal using specific inhibitors of NO synthase (NOS). The objective of this study was to determine directly if the generation of NO is altered in PHT vasculature. Thus, we compared NOS activity in the hyperemic vasculature of normal rabbits and rabbits with PHT (after undergoing partial portal vein ligation). Nicotinamide adenine dinucleotide phosphate diaphorase staining indicated the presence of NOS within the vascular endothelium. Ca(2+)-dependent NOS activity was significantly increased (P < .05) in PHT particulate fractions from the superior mesenteric artery and thoracic aorta, but not from the portal vein. There was no change in NOS activity within the cytosolic fractions. Arterial wall cyclic guanosine monophosphate (cGMP) levels and plasma nitrite levels were both significantly increased in PHT. These results show enhanced NOS activity in PHT hyperemic vessels concurrent with increased tissue cGMP levels. We conclude that enhanced NO synthesis contributes to the hyperdynamic circulation of PHT.

Amino Acid Oxidoreductases↗

PubMed1995

Loss of angiotensin-II receptors in portal hypertensive rabbits.

Decreased splanchnic vascular response to exogenous angiotensin-II (A-II) infusion in portal hypertension has recently been documented. A-II receptor density and binding affinity in the mesenteric artery, portal vein, and adrenal gland of normal and portal hypertensive rabbits were studied. Portal hypertension was induced by partial portal vein ligation 3 weeks before study. There were no significant differences in serum concentrations of sodium, potassium, A-II, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. The portal hypertensive portal vein exhibited a 60% fall in A-II receptor number from 65.1 +/- 0.3 fmol/mg in normal to 27.0 +/- 8 fmol/mg (P < .05) in portal hypertension. A significant decrease in receptor number occurred in the portal hypertensive mesenteric artery, 224 +/- 39 fmol/mg compared with 345 +/- 45 fmol/mg in normal rabbits, and in the adrenal cortex 6.8 +/- 1.3 pmol/mg compared with 12.1 +/- 2.5 pmol/mg in normal controls (P < .05). No significant difference in A-II receptor affinity was observed in tissues studied between normal and portal hypertensive rabbits. Autoradiographic study on A-II receptors was consistent with data from membrane binding assays. Receptor subtype analysis showed exclusive type I receptor binding in the mesenteric artery and portal vein. We conclude there is a global reduction in the A-II receptor number in portal hypertension that may mediate much of the decreased response to A-II seen in this disorder. This loss of the A-II receptor may partially explain hemodynamic derangements peculiar to portal hypertension.

Angiotensin II↗