A rare case of osteoporotic spine fracture associated with epidural lipomatosis causing paraplegia following long-term cortisone therapy.

Cushing's syndrome is frequently associated with osteoporosis. Therefore, the incidence of osteoporotic spine fractures is significant. They are a rare cause of paraplegic syndromes. Additionally, epidural lipomatosis may occur in those patients. The combination of both fracture and lipomatosis may cause neurological deficit. A case of a young patient suffering from drug-induced Cushing's syndrome is reported. She developed progressive paraplegia. Radiographs demonstrated kyphosis of the thoracic spine from T7 to T9 and pathologic fractures. Urgent operation was planned to stabilize and decompress the spinal cord in the area of the kyphosis. Fortunately, magnetic resonance imaging (MRI) was conducted first. It confirmed pathologic fractures of T7-9 but also showed massive epidural fat extending from the level of T1 to T9. As suspected, laminectomy alone in the area of the fracture proved to be insufficient, as shown by myelography during operation. For treatment of paraplegia in this case of symptomatic epidural lipomatosis, an expanded laminectomy was necessary to remove all the epidural fat. Having undergone this procedure, the patient is now recovering from paraplegia. Our experience suggests that care should be taken before operative treatment of patients with pathological fractures in combination with Cushing's syndrome. In addition to vertebral fractures, epidural lipomatosis has to be taken into consideration. Those patients with neurological deficits have to be treated by an extensive laminectomy.

Effect of immunization on gastrin release in rat antrum mucosa.

Helicobacter pylori (H.P.) infection is the main cause of chronic active gastritis and is closely associated with peptic ulcer disease. Chronic hypergastrinaemia is known to be induced in patients infected with this pathogen. Gastrin is the most potent stimulator of gastric acid secretion. In animals infected with H.P. or H. felis vaccination against H.P.can eliminate the bacterium and alleviate associated gastritis. However little is known on the influence of immunization regimes on gastrin release. The aim of this study was to evaluate the effect of systemic immunization on gastrin release in a rat model, using a well defined but for the rat unknown protein. OVA-immunized and non immunized animals received OVA intragastrically in vivo, and serum gastrin was measured. Stimulation with bovine serum albumin (BSA) served as control. In vitro single cell suspensions of the antrum mucosa and mucosal fragments of immunized and non immunized animals were also incubated with OVA and BSA. The results show specific significant gastrin suppression after immunization and antigen feeding. The same results were obtained in the model of mucosa fragments but not in single cell suspensions. This hypothesized that gastric suppression could be mediated by mast cells or T-helper two cells (TH2) in the mucosal layer of the stomach. A single cell suspension is not suitable for studying immunologically mediated gastrin release because direct cell contact is necessary. Further studies with these animal models have to show whether effects seen by vaccination could be mediated by induction of gastrin suppression and studies on human tissues are necessary to show possible similar effects with H.P.

PAF-antagonist administration after hemorrhage-resuscitation prevents splenocyte immunodepression.

A number of studies have suggested that the inflammatory and chemotactic autocoid platelet activating factor (PAF), together with various cytokines, plays an important role in the pathophysiology of trauma, sepsis, and shock. However, little is known about PAF's contribution to the immunosuppression associated with hemorrhage. The aim of our study was, therefore, to determine if the use of a PAF-antagonist following hemorrhage has any salutary effects on splenocyte lymphokine production. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min. The mice were then segregated into three groups and were resuscitated with shed blood plus lactated Ringer's solution (2x the volume of shed blood), containing either a potent PAF-antagonist (Ro 24-4736, a thienodiazepine) in dimethyl sulfoxide (DMSO) or DMSO-vehicle. Sham-operated mice received either DMSO-vehicle in saline or saline alone. Twenty-four hours thereafter the animals were sacrificed and splenocyte cultures established and stimulated for 48 hr with Con A (2.5 micrograms/ml). Supernatant lymphokine levels were determined by bioassay. The cellular release of interleukin-2 and -3 (IL-2 and IL-3) by splenocytes was significantly depressed in the nontreated or vehicle-treated hemorrhaged animals compared to shams. Treatment with the PAF-antagonist Ro 24-4736 restored IL-2 and IL-3 release values to levels comparable to those of the sham-operated animals. Thus, (1) PAF appears to play a significant role in hemorrhage-induced immunosuppression and (2) the use of a PAF-antagonist to uncouple the PAF-generated feedback loops prevents the depression in splenocyte function following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hydroxyethyl starch after trauma-hemorrhagic shock: restoration of macrophage integrity and prevention of increased circulating interleukin-6 levels.

OBJECTIVES: To determine the effects of resuscitation with the colloidal solution (hydroxyethyl starch) vs. crystalloid solution on cell-mediated immune functions after trauma-hemorrhage. DESIGN: Prospective, multiexperimental, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Thirty-six inbred male C3H/HEN (endotoxin-sensitive) mice, aged 6 to 7 wks, and weighing 18 to 23 g. INTERVENTIONS: Crystalloid (lactated Ringer's solution) with and without 6% hydroxyethyl starch after trauma-hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mice underwent laparotomy, were bled to and maintained at a blood pressure of 40 mm Hg for 60 mins, then resuscitated with either 4x the shed blood volume as lactated Ringer's solution or 2x the shed blood volume as lactated Ringer's solution plus 1 x 6% hydroxyethyl starch. Sham mice were neither hemorrhaged nor resuscitated. At 2 or 24 hrs posthemorrhage, serum, splenocytes, peritoneal macrophages, and splenic macrophages were obtained. Bioassays were used to determine interleukin-2, interleukin-3, and interleukin-6 concentrations, while splenocyte proliferation was assessed by 3H-thymidine incorporation. Trauma-hemorrhage markedly depressed splenocyte proliferation, interleukin-6 release by macrophages, and lymphokine release at 2 and 24 hrs postresuscitation. The combination of lactated Ringer's solution and hydroxyethyl starch neither restored, nor exacerbated lymphocyte functions. Interleukin-6 release by peritoneal macrophages was restored 24 hrs after hydroxyethyl starch infusion; serum interleukin-6 concentrations remained at sham levels. CONCLUSIONS: Since the use of lactated Ringer's solution and hydroxyethyl starch after hemorrhage did not adversely affect cell-mediated immune functions, but produced salutary effects on macrophage functions, hydroxyethyl starch is a safe and beneficial resuscitation adjunct.

Dextran 70 administration after trauma-hemorrhagic shock does not impair cellular immune functions.

PURPOSE: Although the effects of the colloid dextran 70 on induction of anaphylactoid reactions or reticuloendothelial phagocytosis have been examined previously, its effects on specific cell-mediated immunity after trauma-hemorrhage shock remain unknown. METHODS: Nonheparinized C3H/HeN mice underwent a laparotomy, were bled, and then maintained at a blood pressure of 35 mm Hg for 60 minutes. Then they were resuscitated with either 4 x the shed blood volume as lactated Ringer's solution (LRS) or 2 x LRS + 1 x dextran 70. Control mice underwent all operative protocols but were neither hemorrhaged, nor resuscitated. At 2 or 24 hours posthemorrhage, serum, splenocytes (SPL), and peritoneal macrophages (pM phi, splenic Mo (sM phi) were obtained. Bioassays were used to determine interleukin-2 (IL-2), IL-3, IL-6, and SPL proliferation. RESULTS: Trauma-hemorrhage markedly depressed lymphokine release, splenocyte proliferation, and IL-6 release at 2 hours after the insult. The combination of LRS + dextran did not restore lymphocyte functions, but also did not further suppress them. The release of IL-6 by pM phi and sM phi at 2 and 24 hours after dextran infusion and serum IL-6 remained at the same level as in LRS-treated animals. CONCLUSIONS: The combination of LRS and colloid dextran 70 does not adversely affect ex vivo cell-mediated immune functions during the first 24 hours after its administration after trauma-hemorrhage. Thus, from the immunological standpoint, dextran is a safe resuscitation adjunct.

Effects of trauma, duration of hypotension, and resuscitation regimen on cellular immunity after hemorrhagic shock.

OBJECTIVE: To determine the effects of: a) surgical trauma, b) crystalloid resuscitation, and c) different durations of hypotension on cellular immunity after hemorrhagic shock. DESIGN: Prospective, multiexperimental, randomized, controlled studies. SETTING: University research laboratory. SUBJECTS: Inbred C3H/HeN (endotoxin-sensitive) mice, aged 6 to 7 wks, weighing 18 to 23 g. INTERVENTIONS: Crystalloid resuscitation, with and without blood, after hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mice which did or did not undergo laparotomy were subjected to hypotension of 35 mm Hg for 60 or 90 mins. Crystalloid resuscitation with and without blood was then provided. Animals were killed at 2 hrs after hemorrhage and cytokine concentrations in supernatants of splenocytes, splenic macrophages, and serum were assessed by bioassays. The cellular release of interleukin (IL)-2, IL-3, IL-6, tumor necrosis factor, and the splenocyte proliferative capacity were significantly and similarly depressed in all groups. Conversely, circulating IL-6 concentrations were significantly increased in all groups. CONCLUSIONS: Cellular immunity was depressed at 2 hrs after simple hemorrhage and no further depression occurred if hemorrhage was coupled with trauma, pure crystalloid resuscitation was provided, or the shock period was prolonged. Thus, the early immunodepression after hemorrhage was mainly dependent on the severity rather than the duration of shock, resuscitation regimen, or tissue trauma.

Noncontact determination of skin blood flow using the laser speckle method: application to patients with peripheral arterial occlusive disease (PAOD) and to type-I diabetics.

The laser speckle method allows the noncontact determination of skin blood flow and its dynamics from a distance of 5 cm. The method is based on the time dependency of the speckle pattern formed by the scattered light of a 5 mW He-Ne laser (632.8 nm). Utilizing the speckle intensity measured through a pinhole, an electronic circuit generates an output signal denoted as blood flow parameter B. All measurements were carried out on the foot dorsum during steady-state, ischemia, and reactive hyperemia induced by a 3-min arterial occlusion. The investigations were carried out in four groups: healthy subjects, asymptomatic smokers, PAOD-patients, and type-I diabetics (D) with severe late complications. As shown by parallel measurements with the tcpO2-method, the initial value Binit of the blood flow parameter B indicates the steady-state blood flow. Binit decreases significantly from 5.95 +/- 2.55 (S.D.) for the control to 4.07 +/- 1.69 (PAOD) and 3.81 +/- 1.51 (D). The half-time BTrh for the increase of B at the beginning of the reactive hyperemia is significantly increased from 4.10 +/- 2.06 s (control) to 14.5 +/- 15.4 s (smokers), 17.6 +/- 32.7 s (PAOD), and 5.31 +/- 3.55 s (D). Other characteristic values such as peak value and time of peak during the reactive hyperemia as well as the final steady-state value and the time of its achievement exhibit similar effects. The correlation coefficients between the different characteristic values obtained from the laser speckle method indicate that the characteristic times of the dynamics and the absolute values of B vary separately and provide supplemental information. A two-dimensional representation of the characteristic values facilitates the differentiation between the four measured groups.

Diabetic microangiopathy in type 1 (insulin-dependent) diabetic patients after successful pancreatic and kidney or solitary kidney transplantation.

To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n = 17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow/velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46 +/- 2 mm Hg to 63 +/- 3 mmHg), reoxygenation time (fall from 224 +/- 12s to 114 +/- 6s) and laser speckle measurement (rise from 4.2 +/- 1.7 to 5.6 +/- 1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation.

Oleic acid induced pancreatitis in pigs.

An experimental model of edematous pancreatitis in pigs was established and measurement of pancreatic macro- and microcirculatory parameters and determinations of pancreatic enzymes (lipase, phospholipase A) and vasoactive mediators (prostanoids, kallikrein, kininogen) were performed. During general anesthesia the pancreas was isolated in situ. Pancreatic microcirculatory parameters were measured using videofluorescence microscopy after iv administration of FITC-Dextran. In hourly collected samples lipase and phospholipase A activities were determined enzymatically, concentrations of kallikrein, kininogen, and selected prostanoids were measured by radioimmunoassay. Two experimental groups were studied: (1) control (n = 9); (2) edematous pancreatitis induced by injection of oleic acid into the pancreatic artery (free fatty acid, ffa; n = 10). The animals were followed up for 6 hr. Systemic hemodynamic parameters remained constant in both groups. In the pancreatitis group pancreatic blood flow and O2-consumption decreased significantly (-55 and -49%), while pancreatic vascular resistance increased significantly (+50%). During baseline conditions 41% of all capillaries were perfused. In the pancreatitis group there were both areas with persistent stasis as well as areas with continuous perfusion. However, in the latter areas the portion of perfused capillaries decreased significantly to 27%. In the control group the portion of perfused capillaries remained constant. Liberation of lipase and phospholipase A especially into lymph and ascites fluid was measured during pancreatitis. Furthermore, considerable releases of kallikrein into lymph (+50%) and ascites (+800%) and a marked consumption of kininogen in lymph (+90%) and in ascites fluid (+80%) were measured. Activation of the arachidonic acid cascade and a significant release of prostacyclin and thromboxane A2 into pancreatic venous blood and lymph was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pancreatic circulation in experimental biliary pancreatitis]. / Die Pankreasdurchblutung bei der experimentellen biliären Pankreatitis.

Measurements of pancreatic micro- and macrocirculation were performed to evaluate the pancreatitis-induced changes. Pigs were anesthetized and ventilated mechanically. Hypotension induced side-effects were avoided by adequate volume replacement. After laparatomy, splenectomy and gastroectomy the animals were enterotomized. Systemic hemodynamic parameters were monitored as well as pancreatic blood flow (Q), which was measured electromagnetically, and arterial and portal-venous blood gases. Pancreatic microcirculatory parameters were observed using fluorescence-videomicroscopy after i.v. administration of FITC dextran 150 and FITC labeled autologous erythrocytes. The pigs were randomly assigned to a control (n = 9) and a pancreatitis group (n = 10), the later being induced by the retrograde infusion of sodium-taurocholate. Systemic and pancreatic macrohemodynamic parameters remained constant in both groups, except for avdO2 and O2-consumption (O2-c) decreasing significantly in the pancreatitis group. At baseline 42% of all capillaries were perfused in both groups. In pancreatitis we detected focal areas with persistent stasis and areas which were continuously perfused. In these areas the portion of capillaries perfused by erythrocytes increased significantly to 67%. This was accompanied by an extravasation of FITC dextran. The finding of an unchanged Q beside reduced O2-c and avdO2 during pancreatitis is explained by the changes in pancreatic microcirculation. Focal stasis was observed beside areas showing typical signs of an acute inflammation: increased macromolecular permeability and capillary recruitment, e.g. oedema and hyperaemia.

Release of arachidonic acid metabolites during acute pancreatitis in pigs.

The pancreatic release of arachidonic acid metabolites was studied in a porcine model of acute pancreatitis. In situ isolation of the pancreatic gland enabled selective collection of pancreatic venous blood, pancreatic lymph, and ascites fluid. Three experimental groups were studied: 1) control (n = 9); 2) hemorrhagic pancreatitis induced by injection of 5% bile salt (sodium taurocholate) into the pancreatic duct (n = 10); and 3) edematous pancreatitis induced by injection of free fatty acid (FFA) into the pancreatic artery (n = 10). Determinations of cyclooxygenase metabolites were performed by radioimmunoassay; lipoxygenase metabolites (LTC4, LTD4) were measured by radioimmunoassay after purification by high-performance liquid chromatography. Prostaglandin (PG)F1 alpha, thromboxane B2, and PGF2 alpha concentrations were almost doubled in the lymph of the FFA group during pancreatitis, as were PGF1 alpha levels in pancreatic venous blood. However, concentrations of cyclooxygenase metabolites remained unchanged in the control group and in the bile salt group. Concentrations of LTC4 and LTD4 in lymph and ascites fluid of both pancreatitis groups increased from about 50 pg/ml to a mean level of 600 pg/ml at 6 h. Leukotriene concentrations in the control group were consistently below 50 pg/ml. The results of this study indicate that above all LTC4 and LTD4 are released from the organ and that these arachidonic acid metabolites may be also involved in the events following acute pancreatitis contributing to the systemic effects of the disease.