Diet, hormonal, and metabolic factors affecting bone mineral density in adolescent amenorrheic and eumenorrheic female runners. Seven adolescent female runners with secondary amenorrhea and six adolescent eumenorrheic female runners received dietary supplements of 1200 mg calcium carbonate and 400 IU vitamin D/d for 12 months. Bone mineral density (BMD) of the axial skeleton was measured by dual photon densitometry at the beginning and end of the 12 month period. Plasma estradiol and ionized calcium concentration were also determined. Bone mineral density decreased in two of the amenorrheic subjects, with the lowest estradiol values concurrent with the severest training regimen and highest calcium intake. There was a significant decrease in plasma estradiol concentration in the amenorrheic runners (p less than 0.05). Plasma ionized calcium and estradiol explained 99% of the variation in BMD (r2 = 0.999). A significant inverse relationship between plasma estradiol and miles run/week was observed (r2 = -0.748). Adolescent female runners who train extensively and have low plasma estradiol levels may be adversely affecting BMD despite supplemental calcium and vitamin D intake.


Effect of treadmill exercise intensity on hepatic glutathione content and its relevance to mammary tumorigenesis. These experiments assessed the role that exercise-induced alterations in glutathione metabolism might play in the acceleration of breast cancer development in rats subjected to nonexhaustive levels of treadmill running. The influence of intensity and duration of treadmill exercise on total and oxidized levels of liver glutathione was evaluated. Nonexhaustive exercise failed to alter the hepatic concentration of total glutathione. However, increasing exercise intensity resulted in tissue accumulation of oxidized glutathione, and an increase in the ratio of oxidized to total glutathione, indicative of an elevated level of intracellular oxidation. Although alterations in glutathione metabolism do not appear to be directly related to the effect of exercise on tumorigenesis, the role of oxidant-induced intracellular damage in this process is being investigated.


The effects of cycling and marathon training on eighteen blood parameters. Abnormal blood chemistry values may be normal for competitive cycling and marathon training, with significant differences (p less than 0.05) between the two groups. The purpose of this study was to examine the effects of bicycle training and marathon training on fasting blood chemistry values. Ten significant differences (p less than 0.05) were observed between cyclists and marathoners on the eighteen blood parameters studied, with four of the blood parameters being outside the established laboratory norms of +/- 2 standard deviations. This was shown by the elevations in creatine phosphokinase levels in the competitive cyclists with the marathoners having higher than the normal ranges for lactate dehydrogenase and lower than normal ranges for hematocrit and red blood cells. Significant differences for albumin, cholesterol, creatine phosphokinase, globulin, hematocrit, lactate dehydrogenase, low density lipoprotein, total protein, red blood cells and triglycerides were observed between the groups.


Hematological status in a group of male athletes of different sports. Suboptimal hematological status has been often recorded in athletes involved in intense physical activity, particularly in middle and long distance runners. It appeared therefore interesting the study and comparison of athletes groups of different sports. One hundred eighty-one male athletes were tested and divided into seven groups according to sport exercise: cross-country skiing, cycling, fencing and tennis (joined together), rowing, running, soccer, swimming. For every athletes erythrocyte and hemoglobin blood concentration, hematocrit, serum iron, transferrin, ferritin and haptoglobin concentration were measured, the mean cell volume and serum iron/transferrin ratio were calculated. Data were compared to find out correlation indices and then grouped according to the practised sport. Statistical indices were computed for each group and for all parameter and analysis of variance was carried out to value the significativity of found differences. The only parameter showing statistically significant differences among groups was the serum level of haptoglobin, with mean value significantly lower in runners. The evidence of this study suggests that individual variability for the remaining parameters exceeds any variation possibly induced by different sport practices.


Acute effect of consumption/omission of breakfast on exercise tolerance in adolescents. The purpose of this study was to determine the acute effects of the consumption or omission of breakfast on exercise tolerance in adolescents. Physically active adolescents (14 males and 21 females) were randomly assigned to receive a breakfast (B) or placebo (P) after an overnight fast. Exercise tolerance tests were done 1.5 hours (test 1) and again 4 hours (test 2) after consuming B or P and consisted of cycling on a stationary bike for 4 minutes at each of four consecutive power settings: 25, 50, 75, and 100 watts. Blood glucose and beta-hydroxybutyrate concentrations were measured before both tests. VO2 and VCO2 were measured during minute 3 of cycling at loads 50 and 75 watts and were used to compute the respiratory exchange ratio (RER). Heart rates (HR) were monitored throughout the test and ratings of perceived exertion (RPE) were made at the end of each 4 min interval. Repeated measures ANOVA revealed that there were no differences in RPE; however, differences for HR and RER did exist. Mean RER values were higher for the males receiving B vs males receiving P during test 1. For females, HR were higher for P compared B, and beta-hydroxybutyrate was significantly elevated for P before test 2. The data suggest that exercise tolerance as indicated by the ratings of perceived exertion are unaffected by prior ingestion of a breakfast but breakfast does affect the physiologic responses to exercise.


Characteristics of women performing strength training: comparison of participants and dropouts. The physiological, anthropometric, personality and lifestyle characteristics of 122 women volunteering for a seven-week program of heavy resistance weight training were studied relative to adherence rates. Initially, volunteers were above-average in body mass and grip strength, but were below-average in chest girth and bicristal diameter. They were also physically active and only 20% smoked. Regular (R) attenders (attendance greater than 80%; 72% of the sample) were physically smaller in terms of stature, mass, girths and dimensions, but had greater strength per kg of mass or LBM compared to participants classified as infrequent (I; 24-76%) and dropout (DO; less than 20%). Conversely, I and DO members were more likely to smoke, to smoke more heavily, to drink coffee and to not eat breakfast. Most dropouts quit during the first week; among volunteers who continued, differences in assigned training intensity had no effect on adherence. Adherence was also unrelated to strength gains, anthropometric adaptations, or injury.


Does cigarette smoking affect the fitness of young adults? Rationale and protocol for future research. While there is considerable evidence of the direct effects of cigarette smoking upon the cardiovascular and respiratory systems, one result of impaired function, that is how cigarette smoking affects fitness and athletic performance, has not been well documented. Because of the potential impact that exercise might have as a substitute for smoking, it is important to delineate relationships, particularly for those who are just beginning to smoke. Literature is presented as a rationale for research in this area and results of a pilot study on smokers and non-smokers are reported. A number of trends in the fitness and pulmonary function tests emerged, suggesting this line of research be pursued.


The effects of positive expiratory pressure on peritoneovenous shunt flow. Cirrhotic patients with peritoneovenous shunts may require mechanical ventilation. Despite the importance of flow to shunt patency and the relevance of intrathoracic pressure to that flow, the relationship between shunt flow and positive airway pressure has not been documented. To study the effects of positive expiratory pressure (PEEP) on shunt flow, models of ascites (n = 8) were created in adult male mongrel dogs. Each animal was anesthetized, intubated, and mechanically ventilated. Peritoneovenous shunts with in-line electromagnetic flow meters were surgically placed. Shunt flow, central venous pressure (CVP), and intraabdominal pressure (IAP) were monitored. Initial intraabdominal pressures were adjusted by infusion of warmed saline and positive expiratory airway pressures were added in increments. Changes in pressures (IAP, CVP) and shunt flow were tabulated and analyzed with linear and polynomial regression. Intraabdominal and central venous pressures increased linearly with PEEP at different rates such that IAP-CVP varied inversely with PEEP. Shunt flow varied inversely as a polynomial function of PEEP. Analyses of these relationships allowed creation of a nomogram which can be interpolated to indicate required intraabdominal pressure needed to maintain shunt flow throughout the clinically useful range of positive airway pressure.


A cost-effective peripheral venous port system placed at the bedside. High costs and a paucity of available operating time have led us to seek alternatives to operatively placed vascular access systems. This prospective study is the initial report of a peripheral port system (P.A.S. PORT System, Pharmacia Deltec, Inc.) placed at the bedside. Seventy-nine patients (52 male, 27 female), ages 3-92 years, had ports implanted by surgical residents with attending supervision. Sixty-eight (86%) received the P.A.S. PORT for long-term antibiotics, antifungal, or antiviral therapy; four (5%) for TPN infusion; three (4%) for blood products; two (3%) for chemotherapy; and two (3%) for iv narcotics. Ports were placed in 10 (13%) HIV(+) patients, three (4%) who were fully anticoagulated, and one who was a hemophiliac with a platelet count of zero. Eight patients (10%) developed superficial phlebitis, all of which resolved with nonsteroidal anti-inflammatory agents within 48 hr without port removal. Seven patients (9%) had their port removed due to infection. The average hospital charge to place the P.A.S. PORT System was $1488.00 vs $2811.00 for a tunneled external chest catheter and $3729.00 for the placement of a chest port. Bedside insertion of vascular access devices can be safely performed with acceptable infection rates allowing more efficient use of hospital operating rooms and with substantial cost savings.


How rapidly do hyperinsulinaemia and hyperglucagonaemia develop after portacaval shunting? Elevation of serum insulin and plasma glucagon have been reported during and immediately after clinical and experimental liver transplantation and in patients with cirrhosis and surgically created or spontaneous portacaval shunts. There is controversy about the relative roles of portal diversion and impaired liver function in the genesis of these elevated levels of pancreatic hormones. End-to-side portacaval shunt was made in normal pigs which were fitted with catheters which allowed transhepatic sampling during and for 4 hr after the operation. Within 5 min of opening the shunt, there was a sixfold increase in portal venous insulin concentrations but hepatic clearance of insulin and the arterial concentration were unaltered. The increase in insulin was sustained for 2 hr. A twofold increase occurred within 1 hr in portal venous glucagon concentration which appeared to be predominantly of pancreatic origin and which continued for the 4 hr of the study. Hepatic glucose uptake did not occur after portacaval shunting despite levels of glucose elevated two-fold by iv infusion. There were no changes in aspartate aminotransferase, hepatic tissue energy charge, or total adenine nucleotides, suggesting that hepatic function was intact. It is concluded that portal diversion results in an increase in insulin and glucagon secretion and in the absence of hepatic uptake of glucose. This is a novel observation with relevance especially in liver transplantation when portal diversion for at least 1 hr forms part of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)


Biochemical analysis of the venous flap in the dog. There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.


Effect of local tumor removal and retained oncolysate on lung metastasis. We reported earlier that oncolysate retained in the excision wound of a local tumor inhibits growth of remote tumor in the rat. We further studied this effect on pulmonary metastasis. C57BL/6 mice were given B16 melanoma F10 cells subcutaneously into the gluteal area (Day 0) and then intravenously on Day 10. On Day 14, mice were divided into four groups. Group 1 received a sham operation and no further treatment. Tumors were excised in the remaining mice. Group 2 received tumor excision alone. Groups 3 and 4 received injections of freeze-lysed tumor cells (TC) and lysate modified (PTC) with a hapten, L-phenylalanine mustard (PhM), respectively, into excision wounds. On Day 24, metastases were assessed by determining metastatic burden. Average diameters of excised tumors in repeated experiments ranged from 8.7 to 10.9 mm. In repeat experiments, pulmonary metastatic burden increased by as much as 52 to 181% in the tumor excised group (Group 2) in comparison with those receiving sham surgery (Group 1). However, metastatic burden was always reduced in Group 3. An even greater reduction was seen in Group 4. To study the possible involvement of macrophages, the production of prostaglandin-E2 (PGE2) and cytotoxicity of macrophages in these animals were examined. It was found that tumor excision enhanced PGE2 production by macrophages and suppressed their cytotoxicity, while TC inoculation prevented both of these changes. An even greater prevention was observed with PTC inoculation. These results indicate an association among macrophage cytotoxicity, PGE2 production of macrophages, and metastasis. In order to clarify the mechanism for these reactions, we did experiments using adherent splenic macrophages from the four groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of laser-assisted fibrinogen bonding on suture material. To evaluate the effect of laser-assisted fibrinogen bonding on the tensile strength of suture material, 10 types of sutures were exposed to various time intervals of diode laser energy after pretreatment with dye-enhanced fibrinogen solder. After exposure, each suture material was stressed on a tensometer and compared with nonlased suture material. Our results indicate that polytetrafluoroethylene suture material was virtually unaffected at all time intervals of exposure to laser energy. Polyester suture material retained 64.3% of its tensile strength at 60 sec of exposure to laser energy. White silk suture material maintained 80% of its initial tensile strength at 60 sec of exposure. These suture materials may be used safely in conjunction with laser-assisted fibrinogen bonding even if prolonged laser exposure is necessary. The other suture materials tested may be compromised significantly by prolonged exposure to laser energy and must be used with relatively shorter irradiation periods.


Results of cholescintigraphy in a VA hospital. In a review of 200 hepatobiliary imaging studies done in a VA hospital over a 5-year period, a sensitivity of 96% and a specificity of 88% were obtained. In a subgroup of 40 patients with alcoholic liver disease, the specificity dropped to 60% although the sensitivity remained high (100%). These data indicated that in patients with alcoholic liver disease a positive DISIDA scan is not diagnostic of acute cholecystitis and cannot be interpreted as an indication for cholecystectomy. Possible modifications of imaging techniques, including delayed imaging and morphine-augmented cholescintigraphy, may prove to increase the specificity of cholescintigraphy in these patients. A prospective study using these modifications would help in determining the current role of cholescintigraphy in the diagnosis of acute cholecystitis in patients with alcoholic liver disease.


Effect of complete cardiac denervation on atrial natriuretic factor release in baboons. We investigated the influence of cardiac innervation on atrial natriuretic factor (ANF) release in baboons. For this purpose, plasma ANF levels were measured in control conditions and in response to head-down (-45 degrees) and head-up tilt (+45 degrees) in six anesthetized baboons before and after complete cardiac denervation obtained by orthotopic autotransplantation of the heart. Cardiac denervation did not modify baseline plasma ANF levels (60.4 +/- 17 pg/ml before and 63.1 +/- 16 pg/ml after heart autotransplantation). In contrast the significant ANF responses to changes in central venous pressure (CVP) induced by postural maneuvers (-45 degrees, + 16.2 +/- 4 pg/ml; +45 degrees, -18.5 +/- 4 pg/ml) were markedly altered after cardiac denervation (-45 degrees, +5.8 +/- 2 pg/ml; +45 degrees, -7.6 +/- 1 pg/ml). The changes in CVP and systemic blood pressure evoked by the postural challenges were comparable before and after cardiac denervation. These results demonstrate that cardiac nerves play a role in the control of ANF release.


Epidermal growth factor accelerates connective tissue wound healing in the perforated rat mesentery. Epidermal growth factor (EGF) has been reported to stimulate healing of wounds in skin, cornea, and gastric mucosa. In the present study, we further investigate the effect of endogenous and exogenous EGF in healing of connective tissue wounds using the rat perforated mesentery model. Healing of mesenteric perforations is accomplished by the connective tissue fibroblasts since there are no interfering variables such as interactions of epithelial cells, desiccation, or foreign materials such as sutures or subcutaneous implants. We performed laparotomy in 114 adult male Sprague-Dawley rats and made 20 standardized perforations in the mesentery of each rat with a scalpel. Rats were randomly assigned to five groups. Group I received no treatment after surgery; Group II received intraperitoneal injections of phosphate-buffered saline (PBS) after surgery and then twice daily for the following 3 days; Group III received 10 micrograms of EGF in the PBS injections according to the same regimen as Group II; Group IV had sham exploration of the submandibular salivary glands; and Group V animals had excision of the submandibular glands 3 days before laparotomy to deprive the main source of EGF in rat. On Days 4 through 10 after surgery rats were sacrificed and the percentage of perforations in each rat which were closed was determined. The curves for the time course of wound closure for Groups IV and V were not different indicating that endogenous submandibular EGF does not play a role in healing of mesenteric wounds.(ABSTRACT TRUNCATED AT 250 WORDS)


Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage. Although hemorrhage depresses splenocyte (SPL) functions and increases susceptibility to sepsis, it is not known whether increased tumor necrosis factor (TNF) or prostaglandin (PG) production are responsible for it. To study this, mice (C3H/HeN) were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 min, resuscitated, and treated with ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage reduced (P less than 0.05) SPL proliferation by 60%, SPL release of interleukin-2 (IL-2) by 47%, interferon-gamma (IFN-gamma) by 67%, TNF by 54%, and interleukin-6 (IL-6) by 46% compared to sham. In addition, splenic macrophage (sM phi) release of interleukin-1 (IL-1) and TNF was decreased by 58 and 67% (P less than 0.05), respectively. However, ibuprofen treatment increased (P less than 0.05) SPL proliferation, lymphokine (IL-2, IFN-gamma, and IL-6) synthesis, and IL-1 release by sM phi compared to hemorrhage alone. Furthermore, ibuprofen enhanced the release of TNF by SPL (+175%, P less than 0.05) and sM phi (+68%) compared to the vehicle group. Ibuprofen also decreased (P = 0.011) the susceptibility to sepsis following hemorrhage. These results indicate that PGs are involved in hemorrhage-induced suppression of cellular immunity and in the increased mortality of such animals following a septic challenge.


DMSO protects against adriamycin-induced tissue necrosis. Inadvertent extravasation of Adriamycin (Adria) can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be the release of free radicals into the tissue. Topical applications of dimethylsulfoxide (DMSO) used after Adria extravasation have been shown to decrease ulcer size. This may be due to DMSO's ability to scavenge free radicals. However, effective topical therapy requires prompt recognition of extravasation, which is often difficult. We hypothesized that the delivery of Adria in low concentrations DMSO would reduce Adria-induced ulcer size and ulcer incidence caused by Adria extravasation. To test this hypothesis, 180, male Sprague-Dawley rats were randomly allocated into three treatment groups of 60 each. All three groups received intradermal injections of Adria (1 mg) diluted in 0.5 cc of saline (Group 1), 10% DMSO (Group 2), or 20% DMSO (Group 3). Rats were observed for 4 weeks. Ulcer incidence (%) and size of ulcers (mm2) were assessed over time. Area of skin ulceration was calculated as the product of the two greatest diameters. Statistical evaluation of the differences in incidence and ulcer size between Group 1 and Groups 2 or 3 were evaluated using analysis of variance. Delivery of Adriamycin in 10 or 20% DMSO resulted in a statistically significant (P less than 0.001) decrease in the incidence of ulceration caused by intentional Adria extravasation.


Roux-en-Y jejunal bypass abolishes postprandial neuropeptide Y release. Numerous physiologic aberrations occur after Roux-en-Y bypass procedures. Neuropeptide Y (NPY), a 36 amino acid polypeptide, has been shown to have many effects on gastrointestinal physiology, including alterations in blood flow, motility, and secretion and absorption. Recent work demonstrating a postprandial increase in circulating NPY prompted this investigation into its potential roles after Roux-en-Y bypass. Three groups of rats underwent Roux-en-Y cholangiojejunostomy, jejunojejunostomy, or proximal jejunal transection with reanastomosis. After a 3-month recovery, the animals were tested with both mixed and fat meals. Control animals had rapid increases in circulating NPY after the mixed meal. This response was not seen in either of the Roux-en-Y groups (P less than 0.05). No animals had circulating changes in NPY after the fat meal. Additionally, small intestinal NPY receptor analysis revealed high NPY affinity to the epithelial cells of the proximal small intestine. Our results demonstrate a dependence of postprandial NPY release on proximal small intestinal continuity that is abolished by Roux-en-Y bypass of a jejunal segment. The absence of postprandial elevation in plasma NPY after proximal jejunal bypass and the abundance of NPY receptors in the proximal small intestine merits further investigation into the physiologic roles of NPY in the foregut.


Effect of glow discharge surface modification of plasma TFE vascular graft material on fibronectin and laminin retention and endothelial cell adhesion. The effects of glow discharge surface modification of plasma TFE vascular graft material (plasma TFE, Atrium Medical Corp., Hollis, NH) on the binding and retention of fibronectin and laminin as well as endothelial adherence were examined. The binding of both fibronectin and laminin to plasma TFE increased as a function of protein concentration in the range of 0.02 to 200 micrograms/ml. Binding to plasma TFE was not saturable in this range of protein concentrations. Fibronectin and laminin binding to plasma TFE was time-dependent, reaching a maximal level (1.8 and 3.2 micrograms/cm2 of bound fibronectin and laminin, respectively) after 30 min (fibronectin) and 4 hr (laminin). Binding was not the result of an accumulation of unbound protein in graft interstices since graft prewetting did not alter the amount of either fibronectin or laminin associated with plasma TFE. In addition, binding was not the result of protein modification during radiolabeling, since unlabeled fibronectin and laminin could compete effectively with their iodinated counterparts for binding to plasma TFE. Dissociation of bound fibronectin and laminin from plasma TFE was rapid, and less than 12% remained bound 60 min after washing. Plasma TFE subjected to glow discharge in O2 and carrying negatively charged functional groups on graft surfaces, exhibited a fivefold increase in fibronectin and laminin binding. In addition, more than 85% of the bound fibronectin and laminin was retained 24 hr after washing. The enhanced retention of fibronectin or laminin by these grafts was associated with an increase in endothelial cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)


Hormonal control of opossum sphincter of Oddi motility: role of myoneural continuity to duodenum. Motilin and caerulein are known to affect motility of the sphincter of Oddi (SO) and the gastrointestinal tract. The role of SO-duodenal myoneural continuity in the action of these peptides was studied. Five opossums had translocation of the duodenal papilla into the jejunum, while preserving the blood supply to the SO and duodenum. Serosal electrodes were placed in the SO, duodenum, and jejunum. Five control animals had electrode placement alone. Myoelectric recording was obtained during fasting and after administration of motilin (400 ng/kg) or caerulein (500 ng/kg/hr). Motilin induced premature phase III-like activity in the SO and intestine in controls. After the translocation of the papilla, the spike frequencies during phase II and phase III were significantly lower than in controls, whereas those during phase I and phase IV were not different. Motilin caused premature intestinal phase III and increased SO spike activity. However, the increase in SO spike activity was insufficient to form phase III. Caerulein produced a sustained increase in spike activity in both regions in both groups, but the increase was less in the translocation group than in controls. These data suggest that duodenal activity stimulated by motilin and caerulein participates in the activation of SO motility via intrinsic myoneural pathways.


Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion. This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow.


Optimal site and amount of splenic tissue for autotransplantation. Clinical and basic studies have documented a high susceptibility to pneumococcal infection in asplenic humans and animals. It has been suggested that autotransplantation of splenic tissue might be a method of providing host resistance when total splenectomy is necessary. However, the effect of splenic autograft has remained controversial. This study was performed to evaluate the most effective site and amount of splenic autograft using rats. Rats were divided into five groups for the purpose of determining the site of splenic autotransplantation: splenectomy, sham operation, implantation into the omental pouch, intraperitoneal implantation, and intramuscular implantation. For determining the amount for autotransplantation, the rats were divided into seven groups: splenectomy, sham operation, and implantations of 25, 50, 100, 200, or 300 mg of splenic tissue. All animals were challenged with Streptococcus pneumoniae type 6, 16 weeks after surgery. Howell-Jolly bodies appeared postsplenectomy, but disappeared in the implanted rats 16 weeks after the operation. Histologically, the implanted tissue was indistinguishable from that of a normal spleen. Pneumococcal clearance from the bloodstream and survival rate were significantly higher in rats implanted in the omental pouch as compared with splenectomized rats. Intraperitoneal and intramuscular implanted rats did not show a significant difference from the splenectomized rats. More than 50% of splenic tissue for autograft showed a significant increase in pneumococcal clearance and survival rate as compared with that of splenectomized rats. It was suggested that the most effective site of autotransplantation is the omental pouch and approximately 50% of the whole spleen would be necessary for prevention from sepsis.


Acceleration of soft tissue repair by a thrombin-derived oligopeptide. Augmentation of thrombin-modulated chemotaxis and mitogenic activity within the early phase of soft tissue repair is now possible. Identification of high-affinity thrombin receptor binding domains within thrombin has enabled the synthesis of a family of peptides which interact with thrombin receptors and enhance in vitro mitogenesis. A single (5.0 micrograms/wound) application of the thrombin receptor-activating peptide (P517-30) significantly increased wound breaking strength from Day 5 (31% over controls) to Day 12. Two models of impaired healing created by radiotherapy (RT) were used to elucidate possible mechanisms of P517-30 action. Although P517-30 did not completely overcome the RT-induced healing impairments, it increased breaking strength under conditions of penetrating whole body RT-induced pancytopenia by 22% and of nonpenetrating surface RT-induced dermal cell damage by 42%. This suggests that P517-30 directly stimulates resident endothelial cells, fibroblasts, or other cells to overcome dermal and circulating monocytic deficits. These results suggest a method to accelerate wound healing with potential clinical applications and emphasize the activity of thrombin as a growth factor.


Lectin histochemical investigations of fetal cultivated pancreatic tissue. The terminal glycoproteins of fetal, cultivated (7-12 days), and adult nondiabetic and diabetic pancreatic tissues (Balb c, C3h mice) were investigated by lectin histology (peanut-, phytohemagglutinin, wheat germ agglutinin, Ulex europeus I, concanavalin A and Ricinus communis agglutinin, PaP method +/- neuraminidase). Anti-insulin and -glucagon were used to identify islet cells. S-100 antibody showed dendritic reticulum cells, anti-IAK proved MHC II antigens (C3h). Cultured tissue was partly incubated with anti-IAK and complement for lysis of MHC II antigens. On the 19th gestational day fetal pancreatic tissue did not bind peanut agglutinin, Phytohemagglutinin, or wheat germ agglutinin, whereas concanavalin A and Ricinus communis were weakly bound. Terminal fucose residues were not expressed by C3h fetal islet cells in contrast to Balb c. Following neuraminidase digestion peanut agglutinin and phytohemagglutinin were strongly bound, indicating sialic acid-substituted terminal glycoproteins. Cultivated tissue (Day 7) bound all investigated lectins (except Ulex europeus I in C3h mice), indicating maturation of islet cells. In spite of the peak of insulin concentration in the medium we observed a faint binding of anti-insulin and investigated lectins following 12 days of cultivation. This indicates a disorder of terminal glycoprotein synthesis at this point. There was no difference in lectin binding patterns of adult nondiabetic islet cells compared to the cultivated tissue (7 days), but no Ulex europaeus I binding of the adult Balb c mice was observed. S-100 binding decreased during the cultivation period as dendritic reticulum cells became destroyed by cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment of experimental liver metastases with a noncontact neodymium: YAG laser. The extent of tumor and liver damage after treatment with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was investigated in a rat tumor model. Colon carcinoma CC531 was implanted in the liver and treated with 60 J (14 tumors), 120 J (15 tumors), or 180 J (12 tumors) at a power setting of 20 W. To assess the effects upon the tissues three animals were sacrificed immediately after treatment and 1, 2, 4, and 8 days later. Sections from the tumor sites were evaluated by light microscopy and the maximal depth and width of different zones of tissue damage were measured. Laser effects could be determined most accurately on Days 1 and 2 after treatment. Multiple linear regression analysis of the data indicated a linear relationship between laser energy and depth of tumor damage (P less than 0.01). The results of this study show the potential of the Nd:YAG laser to produce tumor coagulation necrosis with minimal liver necrosis.


Cholecystokinin does not mediate glucose's cytoprotective effects. Cold restraint stress produces acute gastric mucosal injury in association with altered gastric motility. Enteral nutrients prevent this injury in conjunction with inhibition of gastric emptying. Because cholecystokinin (CCK) is released by nutrients known to be cytoprotective and is thought to inhibit gastric emptying, we performed three experiments to see if CCK contributes to the gastric mucosal protection afforded by enteral nutrients. Our data show that enteral glucose protects the gastric mucosa and increases gastric volume, gastric luminal pH, and gastric mucin. Neither physiologic nor pharmacologic doses of CCK protected the mucosa. None of the other significant effects of glucose on gastric function during cold restraint were affected by exogenous CCK. Furthermore, antagonism of CCK receptors with L-364,718 did not have any independent effects, nor did it diminish the protection associated with enteral glucose. We conclude that enteral glucose protects the gastric mucosa from cold restraint injury in association with a number of potentially beneficial effects on gastric physiology, but none of the effects of glucose in this model appear to be mediated by CCK.


Divergent effects of TNF alpha in the adoptive immunotherapy of a murine sarcoma. We have previously described an in vitro sensitization (IVS) procedure which enabled the generation of therapeutic T cells from tumor-bearing mice for adoptive immunotherapy. The procedure involved culture of tumor-draining lymph node (TDLN) cells with irradiated tumor in the presence of interleukin-2 (IL-2). The availability of many recombinant cytokines affords an opportunity to examine their effects on the immune response to tumor. In this study, we investigated the effect of tumor necrosis factor-alpha (TNF alpha) on the generation and function of IVS cells utilized in adoptive immunotherapy of the murine MCA 106 sarcoma. TNF alpha administered iv at nontherapeutic doses was found to enhance the antitumor efficacy mediated by IVS cells plus IL-2 in the treatment of pulmonary metastases. In contrast, TNF alpha administration to mice bearing progressive footpad tumors had inhibitory effects on the sensitization of tumor-reactive cells in TDLN since IVS cells generated from these animals displayed a diminished antitumor effect. This effect appeared to be due to a reduced number of tumor-reactive lymphoid cells in the TDLN since TNF alpha added to IVS cultures did not alter the antitumor efficacy of the resultant IVS effector cells. These findings indicate the divergent effects of TNF alpha on the immune response to tumor and adoptive immunotherapy with IVS cells.


An improved technique for isolated perfusion of rat livers and an evaluation of perfusates. We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P less than 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion.


Lipopolysaccharide-induced stimulation of alveolar macrophage opsonin-independent phagocytosis. Alveolar macrophage (AM) opsonin-independent phagocytosis may be an important process by which bacteria are cleared from the airspaces. Although it has been shown that clearance of bacteria from the lung is altered in association with endotoxemia, the effect of endotoxemia on opsonin-independent phagocytosis is unknown. Because alterations in AM opsonin-independent phagocytosis could potentially influence bacterial clearance in the lung, we studied the effects of the intravenous injection of Escherichia coli lipopolysaccharide (LPS) into rats on AM opsonin-independent phagocytosis of latex particles. AM obtained by bronchoalveolar lavage (BAL) 2 or 4 hr after injection of LPS demonstrated phagocytosis comparable to AM from control animals. In contrast, AM obtained 12 hr after injection of LPS demonstrated a nearly threefold increase in phagocytosis. Depletion of serum complement with Naja naja cobra venom factor (CVF) did not alter LPS-induced augmentation of phagocytosis. Furthermore, phagocytosis of AM obtained by BAL 2 or 12 hr after activation of complement by injection of CVF was not significantly different from that of AM from control animals, indicating that complement activation alone was not sufficient to stimulate opsonin-independent phagocytosis. These observations suggest that opsonin-independent phagocytosis may represent an important route of bacterial uptake by AM following endotoxemia, and that LPS-induced stimulation of AM opsonin-independent phagocytosis may occur independently of activation of complement by LPS.


Small intestinal submucosa as a superior vena cava graft in the dog. Autogenous spiral vein grafts and ePTFE have been used for reconstruction of the superior vena cava with moderate success. We tested autogenous small intestine submucosa as a superior vena cava interpositional graft in nine dogs. All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by serial venography. One dog died from excessive anticoagulation. Eight dogs were sacrificed at periodic intervals until 72 weeks after surgery. Patent grafts had no evidence of thrombosis, aneurysm, or stenosis. The grafts consisted of dense, organized collagenous connective tissue with a complete endothelial cell layer on the luminal surface. Two dogs are alive at 28 and 34 months after surgery. Graft patency was 89% (eight of nine grafts). We conclude that autogenous small intestine submucosa can be used as a superior vena cava graft in the dog and is worthy of further investigations.


Pretransplant sensitization with major histocompatibility complex class I+ class II- hepatocytes leads to accelerated skin graft rejection. The immunogenicity of major histocompatibility complex (MHC) class I+ class II- hepatocytes is controversial. We studied the effect of pretransplant donor-specific sensitization with either purified hepatocytes (HC) or splenocytes (Spl) on subsequent skin allograft survival. Five million Percoll-purified DBA HC or 10 x 10(6) DBA Spl were injected into C57BL/6 recipients either intraperitoneally (ip) or into a sponge matrix allograft. Twelve days later, sensitized mice received a DBA skin graft. On the same day, allogeneic (DBA) and syngeneic (BL/6) skin grafts were placed on naive BL/6 mice. In naive BL/6 mice, allogeneic skin graft survival was 7.8 +/- 0.5 days (n = 4), and syngeneic survival was indefinite (n = 5). Skin graft survival (mean +/- SD in days) in recipients sensitized with hepatocytes ip was 6.0 +/- 1.2 days (n = 5) compared with 5.6 +/- 0.5 days in recipients sensitized with splenocytes ip. Similarly, graft survival in recipients that received hepatocytes into a sponge matrix allograft was 5.67 +/- 1 days (n = 6) compared with 5.2 +/- 1.1 days (n = 8) in those that received splenocytes into the sponge. There was no difference in graft survival between mice sensitized with HC vs Spl, nor between mice injected ip vs with the sponge. All sensitized mice experienced accelerated graft rejection compared with naive controls (P less than 0.000). These results demonstrate that purified MHC class I+, class II- murine HCs are immunogenic in vivo. Sensitization with donor-specific HCs led to accelerated rejection of subsequent skin grafts, similar to the accelerated rejection seen after sensitization with MHC class I+ and class II+ splenocytes.


Identification of a novel cell population in nonhealing wounds in tumors. We have explored wound healing in tumors as a possible model for tumor-host interaction. This work demonstrated tumor wound healing failure to be the result of intense inhibition of fibroblasts although the tumor cells did not appear to be the direct source of the inhibitors. The inflammatory infiltrate found in tumor wounds was then examined for possible sources of the observed fibroblast suppression. Although the tumor wound infiltrate contains cell populations similar to a normal wound infiltrate, it also contains a large, vacuolated, nonadherent, phagocytic mononuclear cell which has morphologic and cytochemical characteristics of a lipid-laden macrophage. However, the cell also proliferates under normal culture conditions and has an immunophenotype more characteristic of lymphocytes than those of macrophages with striking expression of the CD8 surface antigen. Conditioned media from this cell population markedly inhibit fibroblast proliferation suggesting it is the source of fibroblast inhibitors within the tumor wound. Mechanical dissociation of non-wounded tumors yielded evidence that the tumor wound cell is normally present in small numbers within the tumor.


Suramin interference with transforming growth factor-beta inhibition of human renal cell carcinoma in culture. Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.


Intratumoral rIL2-based immunotherapy in B16 melanoma. Limiting factors in systemic recombinant interleukin-2 (rIL2) therapy may be overcome by intratumoral (IT) administration. A series of experiments was conducted to assess the efficacy of IT rIL2 alone and in combination with LAK cells and IFN-gamma. C57BL/6 mice bearing B16-F10 subcutaneous tumors were randomly assigned to treatment groups including: noninjected controls, IT placebo (NaCl, D5W), IT bovine serum albumin (BSA), IT rIL2 (centrally and peripherally), IT rIL2/LAK, IT rIL2/IFN-gamma, and intraperitoneal (IP) rIL2. A tumor size-dependent dose of cytokine was injected daily and LAK cells were given weekly. Systemic immune response was assessed by splenocyte mitogenesis and T-cell subset distribution using thymidine radioassay and flow cytometry, respectively. In terms of survival and tumor growth rate, IT rIL2 was superior to noninjected control, IT placebo, IT BSA, and IP rIL2 (P less than 0.05). The addition of IT LAK cells conferred no therapeutic advantage. The combination of rIL2 and gamma IFN-gamma had a slight survival benefit over rIL2 alone (30.8 days vs 20.4 days). Histologic analysis demonstrated an increase presence of intratumoral macrophages in the IT rIL2-treated tumors (P less than 0.05). Lymphocyte mitogenesis and L3T4+ subset were not altered by any treatment. In vitro thymidine uptake by tumor cells was not affected by rIL2 nor IFN-gamma alone but the combination of rIL2 and IFN-gamma resulted in significant tumor cell growth inhibition. Spontaneous lung metastases were more prevalent following central IT rIL2 (75% vs 29%, P = 0.07) not accountable by needle trauma but avoidable by the use of peritumoral injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Contrast-induced nephrotoxicity: the effects of vasodilator therapy. The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with peripheral vascular disease has generated concern about the incidence and avoidance of contrast-induced nephrotoxicity (CIN). In this prospective study, we sought to identify those patients at greater risk of developing CIN and to evaluate the efficacy of vasodilator therapy with dopamine in limiting this complication. Baseline serum creatinine (Cr) concentrations were obtained on admission and daily for up to 72 hr after angiography in 222 patients undergoing 232 angiographic procedures. The preangiographic treatment was varied at 2-month intervals for 1 year. All patients received an intravenous infusion of 5% dextrose and 0.45% normal saline at a rate of 75 to 125 ml/hr. During the first interval patients received 12.5 g of 25% mannitol immediately prior to their contrast load, in addition to intravenous fluids. During the next 2-month period the patients were given renal dose dopamine intravenously (3 micrograms/kg/min) commencing the evening before angiography and continued to the next morning. During the latter half of the study the treatment regimens were modified so that the use of mannitol was restricted to patients with diabetes mellitus and dopamine to patients with serum creatinine concentrations of > or = 2 mg/dl. Postangiographic elevation in Cr occurred in 2, 10.4, and 62% of studies in patients with baseline creatinine levels of < or = 1.2 mg/dl, 1.3 to 1.9 mg/dl, and > or = 2.0 mg/dl, respectively. None of the patients receiving dopamine experienced an elevation in creatinine. There was no statistical correlation between age, diabetes, or medication with calcium channel blockers and CIN.(ABSTRACT TRUNCATED AT 250 WORDS)


Problem-based learning: an effective educational method for a surgery clerkship. Problem-based learning (PBL) has been implemented during the clinical years in a few medical schools. The purpose of this study is to determine whether PBL provides a better education than traditional methods. Students in the first and third rotations (n = 42) went through the traditional clerkship, which utilized Socratic teaching (SI), while students in the second and fourth rotations (n = 36) were taught by the PBL method. Two performance measures were used to assess clerkship effectiveness. One was a modified essay examination (MEE) administered as part of the departmental evaluation. The other was the NBME-II exam and its surgery subsection NBME-II-S. The MEE was designed to measure six dimensions of the problem-solving process. The NBME-II was utilized to measure knowledge. Unpaired t tests were used to identify statistically significant group differences. The PBL group performed significantly better on two MEE dimensions: (1) differential diagnosis formation (PBL, 92.5 +/- 0.8; SI, 89.1 +/- 0.5; P < 0.01) and (2) interpretation of clinical data (PBL, 93.3 +/- 0.6; SI, 91.6 +/- 0.4; P < 0.03). A third dimension, ordering appropriate lab and diagnostic studies, approached significance (P = 0.057), and the PBL group performed better. On the NBME-II there was not a significant difference between the two groups. However, the trend (P = 0.059) was for the PBL group to score higher on the NBME-II-S (PBL mean: 502 +/- 15; SI mean: 468 +/- 12). When overall achievement was controlled for, the PBL group performed significantly better than the SI group (P = 0.046) on the NBME-II-S.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolation and characterization of rabbit cardiac endothelial cells: response to cyclic strain and growth factors in vitro. Studies of the cardiac endothelium have been complicated by difficulties in isolating and maintaining cardiac endothelial cells (EC) in culture. We present in this paper a method of obtaining pure EC from rabbit hearts by collagenase digestion and membrane filtration. Pure cultures of EC displaying characteristic EC morphology, uptake of di-I-acetylated LDL, and contact-inhibition of growth were successfully maintained in culture for several weeks in media supplemented with fetal bovine serum, bovine retina-derived growth factor (RDGF), and antibiotics. Since EC in vivo are exposed to a complex pattern of physical forces we also sought to determine the proliferative response of cardiac EC subjected to pulsatile strain in vitro and compared it with the response to the addition of an exogenous growth factor, RDGF. The results demonstrate that a regimen of 60 cycles per minute, 24% cyclic strain induced a significant increase in cardiac EC proliferation and suggests that physical forces may have a trophic effect on EC proliferation.


Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury. Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness.


Amino acid substrate preloading and postischemic myocardial recovery. During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.


Diphenylhydantoin inhibits calcification of bovine pericardial implants and myocardium: a preliminary study. Calcification is a major cause of glutaraldehyde-fixed bioprosthetic valve failure. Recent studies have shown that dystrophic calcification shares basic features with normal bone mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. In this study, we observed that calcification of the myocardium of DBA/2J mice was inhibited or reversed by diets supplemented with 100 mg/kg diet diphenylhydantoin (dilantin) for 70 days, with a calcification incidence of 25% in the dilantin group versus 58% in control. We further studied the effects of dilantin on bioprosthetic valve calcification. Three groups of young male Sprague-Dawley rats (100 g, 9/group) were implanted subcutaneously with 1-cm2 pieces of glutaraldehyde-fixed bovine pericardium. Controls were fed a ground chow for 45 or 90 days postimplantation; experimentals received the same chow for the first 45 days postimplantation and then were fed the same diet supplemented with 1000 mg dilantin/kg for the succeeding 45 days. Calcium content (microgram/mg dry weight) of the implants in the dilantin group was 137 +/- 18.6 versus 214 +/- 34.3 in 90 days control and 79.9 +/- 41.5 in 45 days control (mean +/- SD, P < 0.01 and P < 0.05 respectively, t test). The tibia calcium content of the dilantin group was not significantly different from 90 days control. We conclude that orally administered dilantin inhibits calcification of glutaraldehyde-fixed bovine pericardial implants preferentially. It does not cause decalcification either of implants that have already calcified or of the bones. The anti-calcification effect of dilantin may be associated with its anti-vitamin D effect.


Fibrinolytic drugs prevent pericardial adhesions in the rabbit. Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically.


Optimal method for culturing vascular prosthetic grafts. Vascular prosthetic infection may be underrecognized when identified by standard culture techniques. Improved microbiologic methodology may enhance detection of bacteria in prosthetic graft specimens, and thus may alter clinical decisions. Quantitative culture techniques were employed to compare three methods of enhancing bacterial recovery from Dacron graft cylinders seeded with commonly encountered bacterial pathogens. Methods included: (1) ultrasonic bath treatment, (2) direct ultrasonic disruption, and (3) agitation on a Vortex mixer. Ultrasonic bath treatment released bacteria with colony counts that were consistently greater by 1 log than direct ultrasonic disruption and Vortex agitation. Direct ultrasonic disruption at high energy levels selectively killed gram-negative bacteria by as much as a 4 log decrease in viable organisms. Agitation (Vortex mixing) of the specimen produced the lowest counts among the three methods tested. These data would indicate that a 5-min ultrasonic bath treatment was the optimal method of preparation of vascular prostheses for bacterial culture.


Magnetic resonance imaging of small arteries. Magnetic resonance imaging (MRI) with receive-only surface coil technology was used to visualize and quantitative luminal diameters of small arteries in the rat. MRI measurements of normal and aneurysmal aortas, over a diameter range of 1-3 mm, were closely correlated with direct measurements made visually at laparotomy: measured differences averaged 0.16 mm, and the least-squares regression line (R2 = 0.97, P < 0.001) compared favorably to the line of equivalence, X = Y. This noninvasive but precise imaging modality demonstrates the potential value of using MRI to evaluate the diameter of small vessels, including the postoperative monitoring of arterial bypass graft patency in peripheral regions.


Human gallbladder bile becomes lithogenic during short-term intravenous hyperalimentation. Biliary sludge formation is reported to be one of the complications of intravenous hyperalimentation (IVH); however, the change in human biliary lithogenicity during IVH treatment has been little studied. To clarify the pathogenesis of IVH-induced biliary sludge, we determined biliary lipid composition, vesicular cholesterol concentration, and nucleation time using gallbladder bile samples collected from three groups: The IVH group comprised 9 patients who received IVH with fasting for a period of 2-8 days prior to surgery for gastrointestinal diseases. The control group comprised 10 patients operated after overnight fasting for gastrointestinal diseases. The cholesterol gallstone group comprised 14 patients surgically treated for cholesterol gallstone disease after overnight fasting. The nucleation time in the IVH group was significantly shorter (7.8 +/- 5.3 days, mean +/- SD) than that in the control group (17.3 +/- 5.5 days), while it did not reach the value in the cholesterol gallstone group (3.1 +/- 3.3 days). The cholesterol saturation index in the IVH group (1.01 +/- 0.27) was higher but not significantly different compared with the control group (0.80 +/- 0.21). The concentrations of biliary lipids and individual bile acid were similar in the IVH and control groups. The vesicular cholesterol concentration in the IVH group (3.0 +/- 2.1 mM) was significantly higher than that in the control group (0.9 +/- 1.0 mM). In conclusion, IVH with fasting causes a rapid cholesterol nucleation time and a higher vesicular cholesterol concentration, thereby inducing an initial stage of gallbladder sludge formation.


Hypothermia relieves oxidative stress in reperfused skeletal muscle following partial ischemia. The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference (Em) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups (N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15 degrees C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting Em (-mV) was significantly depolarized (P < 0.05 versus baseline) in control (74.9 +/- 0.8 from 91.0 +/- 0.1), hypothermia (64.4 +/- 1.1 from 90.9 +/- 0.3), and hypothermia-sham (67.2 +/- 1.4 from 90.9 +/- 0.4) animals. Upon reperfusion, resting Em remained depolarized in control animals (74.7 +/- 1.6), while repolarization occurred in hypothermia (88.8 +/- 1.1) and hypothermia-sham (90.7 +/- 0.3) animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Aortoiliac reconstruction following penetrating injury. In summary, there are several factors essential to successful treatment of major vascular abdominal injuries. Prompt resuscitation and abdominal exploration is paramount. Proximal control can quickly be obtained at the esophageal hiatus and adequate exposure of the retroperitoneum is mandatory. Most aortic injuries can be repaired primarily; however, if an arterial substitute is necessary, then PTFE is the substitute of choice. Reimplantation of the injured iliac artery to the contralateral iliac artery is an option for bifurcation injuries if that will not inordinately constrict the lumen. And finally, four-compartment fasciotomies will decompress the lower extremities and prevent ischemic muscle necrosis following reperfusion injury.


Cognitive and attitudinal factors in the analysis of alternatives to drunk driving. The present study examined cognitive and attitudinal factors relevant to drunk-driving tendencies in individuals having zero, one and multiple drunk-driving convictions. Results indicate that the awareness of consequences of being in an accident was related to driving record but not to drunk-driving tendencies. In contrast, the awareness of consequences of being arrested for drunk driving (e.g., receiving fines, having one's name appear in the news and having a criminal record) was negatively related to drunk-driving tendencies. Attitudes toward alternatives to drunk driving (e.g., take a taxi, call a friend) were also negatively related to drunk-driving tendencies. The findings are discussed with respect to developing prevention programs.


The limited utility of BAC for identifying alcohol-related problems among DWI offenders. To see if blood alcohol concentration (BAC) is a significant indicator of problem drinking or an alcohol-related diagnosis, the relationships between BAC at arrest for drinking and driving, typical drinking, alcohol-related problems, problem drinking and an alcohol abuse or dependence diagnosis were examined for 235 drinking and driving offenders referred for alcoholism evaluation. BAC and typical drinking correlated weakly and no significant relationship between alcohol-related problems and BAC was found. Further, no significant relationship was found between BAC and alcohol abuse or dependence diagnoses, or between problem drinking and BAC. These findings cast doubt on the usefulness of a single report of BAC for diagnostic and screening purposes.


Drinkers and their driving: compliance with drinking-driving legislation in four Australian states. This study replicates work in Norway and the United States in investigating the extent to which Australian drivers attempt to comply with drinking-driving legislation. In a four-state survey of 1,133 drinkers, it was found that people were aware of the need to control their alcohol input before driving, and derived estimates of blood alcohol after a recent away-from-home drinking occasion demonstrated that the amount people drank was influenced by whether or not they were driving. Drivers reported drinking less than nondrivers and were also those who usually consumed less alcohol. These findings were also true of people with different levels of normal consumption. Although these results are encouraging, it is suggested that there is need for further modification of sanctions, and that the community needs more information about the alcohol content of drinks and drink sizes if people are to moderate effectively their drinking before driving.


Citation analysis of 541 articles published in drug and alcohol journals: 1984-1988. Citation histories of 541 articles published in 1984 in 12 drug and alcohol journals were followed through 1988. Considerable variability in mean citation rates across journals was observed. The mean citation rate for the 541 articles was 3.48. Approximately 71% of the articles examined were cited at least once between 1984 and 1988. The present findings suggest that articles published in drug and alcohol journals may be cited more frequently, and exert their influence longer, than those of the social science literature generally. Qualitative analyses suggest that methodological and review articles tend to be cited most frequently. The need for a comprehensive scientometric examination of the drug and alcohol literature is emphasized as is the potential role of multivariate techniques in the identification of variables predictive of individual article and journal citation rates.


Self-efficacy, aftercare and relapse in a treatment program for alcoholics. The role of self-efficacy in the prediction of relapse following alcoholism treatment was examined in a 12-month follow-up evaluation. Self-efficacy was assessed at intake to inpatient treatment and again at discharge. The drinking status of male alcoholics completing treatment then was assessed during six intervals over the course of the posttreatment year. Results indicated a significant increase in self-efficacy from intake to discharge. Additional analyses showed that lower intake self-efficacy ratings were associated with relapse by either 6- or 12-months posttreatment. Discharge self-efficacy, on the other hand, was not related to relapse status at either posttreatment point. A subsequent analysis of the pattern of relapses across the six follow-up intervals was conducted using survival analysis. Results revealed that only intake self-efficacy was predictive of the follow-up interval during which a relapse occurred. Individuals high in self-efficacy at intake showed the greatest resistance to relapse across time. The maintenance of aftercare further reduced the risk of relapse. The results are discussed with respect to self-efficacy theory and the problem of ceiling effects in posttreatment self-efficacy assessments.


A 10-year follow-up survey of acceptability of controlled drinking in Britain. This study was designed to reassess the acceptability of controlled drinking (CD) approximately 10 years after Robertson and Heather's (1982) survey of British treatment providers. Sixty percent of a wide range of almost 300 targeted alcohol service agencies in Scotland, England and Wales responded to a mailed questionnaire. Three-quarters of these respondents reported that nonabstinence was an acceptable outcome goal. About half of the respondents who accept CD reported it as acceptable for only 1-25% of their clientele. Within the subgroup of outpatient agencies, almost one-third reported CD as appropriate for at least 50% of their clientele. Respondents endorsing CD rated severity of dependence, client attitudes and beliefs about controlled drinking and abstinence, drinking history, liver function test results and social stability/social relationships as the most important factors of those listed in selecting outcome goals. Respondents reportedly based acceptance or rejection of CD most frequently on their own professional experience and, to a lesser extent, on research evidence for or against CD and on agency policy.


Stages of progression in drug involvement from adolescence to adulthood: further evidence for the gateway theory. Sequential stages of involvement in alcohol and/or cigarettes, marijuana, other illicit drugs and medically prescribed psychoactive drugs from adolescence to adulthood are investigated in a longitudinal cohort that has been followed from ages 15 to 35. Alternative models of progression are tested for their goodness of fit. Four stages are identified: that of legal drugs, alcohol or cigarettes; marijuana; illicit drugs other than marijuana; and medically prescribed drugs. Whereas progression to illicit drugs among men is dependent upon prior use of alcohol, among women either cigarettes or alcohol is a sufficient condition for progression to marijuana. Age of onset and frequency of use at a lower stage of drug use are strong predictors of further progression.


Gender patterns in consequences of collegiate alcohol abuse: a 10-year study of trends in an undergraduate population. Although college men have typically reported significantly more alcohol problems than women, debate about a possible convergence of gender differences has emerged in recent years. Time trend data on gender differences based on consistent measures of alcohol-related problems are scant, however. Another limitation of previous research has been the predominant focus on alcohol problems most common among men. This article provides data on gender differences and trends in several types of negative consequences of student drinking in a collegiate population from four surveys conducted between 1979 and 1989. The data do not support an overall "convergence hypothesis" as men remained much more problematic in several types of consequences-specifically abuse problems that are public, involve legal repercussions, or that endanger others. Consequences that are more personal or less prone to provoke public response reveal little or no gender differences, however, in the most recent collegiate cohorts. Thus, more gender research is needed on types of alcohol problems in campus context.


Cirrhosis mortality and occupation.

Cirrhosis mortality and occupation. Cirrhosis, the ninth leading cause of death in the United States, has been associated with abusive alcohol consumption patterns. Since the workplace serves as a major exposure variable for alcohol consumption over a significant portion of the lifecourse, and since heavy drinking has been shown to differ by type of occupation, this study examines the relationship between type of occupation and cirrhosis mortality. The California Occupational Mortality Study data set (1979 to 1981) provided the information on primary occupation and liver cirrhosis mortality. Crude and sex-specific mortality rates were calculated based on information from a 20% sample of the 1980 California census (included in the data set). Ninety-five percent confidence intervals were calculated around all rates to determine if any were significantly different from rates for the entire state. The findings uphold the view that an association exists between occupation and cirrhosis mortality. The highest mortality rates were found among persons with blue-collar type jobs (e.g., construction laborers and machinists) or jobs where alcohol was easily available (e.g., bartenders and waitresses). Future research needs to specify the factors associated with occupation that may promote the chronic heavy drinking that leads to cirrhosis.


Assessment of alcohol-related workplace activities: development and testing of "Your Workplace". Alcohol-related workplace activities are assessed using a short, easy to administer, self-report instrument. Three scales--Adverse Effects of Drinking on Work Performance, Support for Consumption and Support for Abstinence--are derived from it. They have internal reliability, are independent of one another and have face validity as well as discriminant and convergent validities. Some evidence of predictive (criterion-related) validity is presented. Researchers seeking to assess the interrelationship between alcohol-related work factors and drinking behavior can apply this instrument to the task.


Measuring quantity and frequency of drinking in a general population survey: a comparison of five indices. This article compares five indices of alcohol consumption in a general population survey conducted in 1985 in the Netherlands. Self-reports of consumption were obtained with a prospective diary, a retrospective 7-day recall method, and three summary measures, such as a quantity-frequency index. The coverage of sales data appeared highest for the diary (67%), which suggests a higher validity. Special attention was given to comparisons of quantity and frequency of drinking between the diary, on the one hand, and the weekly recall and summary measures, on the other. It was found that underreporting, relative to the diary reports, was generally higher in the frequency than in the quantity domain. This result, together with the finding from longitudinal studies that intraindividual variation is also higher for drinking frequency, leads to the conclusion that forgetting is a potent source of undercoverage in surveys and to the hypothesis that large differences in overall drinking pattern between populations (e.g., in regularity of drinking) may account for the large differences in coverage rates of sales data. Furthermore, the subjectively assessed probability of drinking by means of a "usual" frequency question appeared a poor predictor of (diary) drinking frequency for respondents reporting a low or moderate frequency. For subjects claiming a high "usual" drinking frequency, a reasonable correspondence between diary and summary measures was found. This mitigates the fear often expressed that heavy drinkers particularly underreport their consumption.


Alcohol availability and consumption: Iowa sales data revisited. Recent changes in Iowa liquor control laws ended the 51-year-old state alcohol monopoly distribution system and turned the sales of bottled wine and spirits over to the private sector. The resulting increase in the availability of these beverages provided a unique opportunity to study the relationship between increased wine and spirits availability and changes in their consumption. Time series analyses of monthly sales (apparent consumption) trends showed that the increased availability had no lasting impact on consumption.


The relationship between license type and alcohol-related problems attributed to licensed premises in Perth, Western Australia. Drink-driving offenses, alcohol-related traffic accidents and number of assault charges were used as indicators of the degree of alcohol-related problems associated with individual licensed premises in the Perth Traffic Police region of Western Australia. These indicators were used to rank five main categories of licensed premises according to the levels of harm experienced by their customers while controlling for the amounts of alcohol sold in each category. Nightclubs, taverns and hotels emerged as "high-risk" in comparison with clubs and restaurants. The role of such factors as different customer characteristics, opening hours, types of entertainment, restrictions on clientele and provision of meals are discussed as possible explanations underlying this finding.


The effects of alcohol on the cardiovascular stress response in men at high risk for alcoholism: a dose response study. Men at risk for alcoholism appear to be cardiovascularly hyperreactive to stressors; high doses of alcohol have been found to significantly dampen this hyperreactivity. The present study examined the effects of various doses of alcohol on cardiovascular reactivity in high- versus low-risk men. Cardiovascular reactivity to a stressor (unavoidable shock) was examined in men with multigenerational family histories of alcoholism and in family history negative men while they were sober and after they had consumed one of five alcohol doses (active placebo, 0.50, 0.75, 1.00 or 1.32 ml 95% USP alcohol/kg body weight). No significant placebo effects were observed in the active placebo condition. Furthermore, the cardiovascular reactivity dampening effect in high-risk men was evident only at moderate to high doses of alcohol, suggesting that men at high risk for the development of alcoholism must consume moderately high doses of alcohol in order to obtain this potentially reinforcing consequence.


Resistance to alcohol impairment of visual-motor performance: does it help to pay attention? In a 2 x 2 factorial design, moderately intoxicated (BAC = .05) college students (n = 40) were exposed to a cognitive set (to concentrate) and/or an auditory feedback signal while performing a modified pursuit-rotor task across five postbeverage trials. Self-reported "highness" was also assessed. A control group received placebo drinks and performed without aids. Hypothesized main effects for both set and signal revealed that intoxicated aided subjects outperformed their unaided counterparts. Moreover, subjects who received both aids outperformed all other intoxicated subjects and performed equivalently with unaided placebo subjects. Separate analyses of the first postbeverage trial and use of covariance analyses provided confidence that the obtained effects were not attributable to acute or chronic tolerance. Highness correlated negatively with performance; but set and signal effects on highness failed to reach significance. Although alcohol-induced motor impairment is not recognized in the research literature as being under volitional control, subjects in the present study exhibited clear resistance to alcohol impairment. Possible psychological mediators and moderators of the obtained effects are discussed, as well as the relevance of these findings for tolerance research. Practical implications are also considered.


Resource-limited information processing in alcoholism. A concurrent-task paradigm was utilized to examine the availability of limited-capacity information-processing resources in long-term chronic alcoholism. Normal control subjects and detoxified long-term alcoholics did not differ in their performance of a primary task that required an assessment of the meaning of foveally-presented words. However, reaction time measures indicated that the abstinent alcoholics were relatively impaired in their ability to concurrently perform a secondary task that required them to detect randomly-occurring and spatially-distributed visual probe stimuli. This impairment is interpreted as reflecting an abnormal limitation in the attentional resources abstinent alcoholics have available for task performance. The relationship between this deficit and the types of biological abnormalities and neuropsychological impairments commonly observed in alcoholism is discussed.


Ultrastructural alterations in ileal M cells of rats after chronic ethanol ingestion: reversal after cessation of ethanol. Membranous (M) cells within the dome epithelium of ileal Peyer's patches have been shown to provide selective antigen entry for mucosa-associated lymphoid tissue. This study produced morphologic evidence of ethanol-induced disruption of the architecture in follicle-associated epithelium. The adherens type junctions of the lateral plasma membranes between M cells and columnar absorptive cells were disrupted. A 45-day exposure by ingestion of ethanol also produced marked changes in the ultrastructure of M cells. All experimental animals showed mitochondrial swelling with loss of matrix density, dilation of the endoplasmic reticulum and cytoplasmic vacuolization. The ethanol content of serum and chyme samples were 180 mg/dl and 160 mg/dl, respectively. This was well below the 4,280 mg/dl of the diet therefore a systemic mechanism was implicated for the changes observed. Membranous cells from the recovery group were normal 15 days after withdrawal from ethanol. We concluded that the ethanol-induced cytopathology in ileal M cells is reversible when ethanol exposure is discontinued.


Prognostic factors for noncurative gastric cancer: univariate and multivariate analyses. We performed univariate and multivariate analyses of possible prognostic factors related to postoperative clinical course of patients with advanced gastric cancer. Noncurative resection was done for 119 patients with hepatic metastasis, peritoneal seeding, extensive lymph node metastasis, or direct invasion to adjacent organs, either alone or in various combinations. In the univariate analysis, 6 of 17 items such as peritoneal seeding, lymphatic invasion, vascular invasion, mode of invasion, extent of lymphadenectomy, and width of serosal invasion significantly correlated to the prognosis. The multivariate analysis indicated that three inherent pathologic factors, mode of invasion, lymph node metastasis, and hepatic metastasis, and one treatment factor, extent of lymphadenectomy, were significant variables predictive of the prognosis and that the prognosis was expected to be very poor in cases of infiltrative type, nodal involvement to tertiary nodes, presence of hepatic metastasis, and lymphadenectomy less than R3. Prognosis in terms of the extent of lymphadenectomy shows that extensive lymphadenectomy (R3) proved to be significantly effective in prolonging survival time, even after noncurative gastrectomy. We recommend extensive lymphadenectomy to prolong survival time for such patients.


Skeletal metastasis from occult carcinoma. We reviewed 177 patients with skeletal metastases, seen between 1984 and 1989, to define the characteristics of metastatic bone disease from an occult primary carcinoma. In 52 (30%) patients, the primary carcinomas could not be identified when the bone metastases were first diagnosed. This group was predominantly male, with intractable pain the most common symptom. The primary tumors were identified on antemortem evaluation in 28 (54%) patients after extensive examination. Among these, the primary tumor was in the lung in 9 patients, followed by liver (8), kidney (5), prostate (3), thyroid gland (2), and rectum (1). The identifiable occult malignancies possessed three common features: all were osteophilic tumors, all had a high incidence in the specific geographic area, and all were not amenable to early detection. The mean survival of these patients was 11 months. Current treatment modalities failed to affect the course of these patients, except for those with primary carcinomas of the kidney and prostate. This observation attests to our limitations in both the diagnosis and treatment of this problem. Efforts should be directed primarily toward excluding those common and/or treatable tumors only.


Early gastric cancer: an analysis of 44 cases with emphasis on the prognostic significance of the macroscopic and microscopic growth patterns. Forty-four consecutive cases of "early gastric cancer" were studied according to the macroscopic classification proposed by the Japanese Gastroenterological and Endoscopy Society and further analyzed in terms of growth patterns. The tumours were then classified into the small mucosal type, the superficially spreading (Super) type and the penetrating growth (Pen) type. The Lauren type (intestinal vs. diffuse), presence of lymphatic and venous invasion, and lymph node metastasis were also assessed. Most elevated tumours showed a superficial growth pattern and were classified as Lauren's intestinal type, whereas depressed lesions were associated with submucosal invasion and were classified as diffuse. Microscopic patterns did not show any correlation with Lauren's classification. Mean duration of follow-up was 67.8 months and the overall actuarial survival was 93%, 80%, and 72%, at 2, 5, and 10 years, respectively. Aside from venous invasion no correlation was found between survival and any of the morphological parameters analysed.


Hepatic resection following systemic chemotherapy for metastatic colorectal carcinoma. Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 11 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients.


Therapeutic gain of local and radical resection combined with postoperative radiation for murine fibrosarcomas. Resection of 8-mm fibrosarcomas (FSaII) growing in the right leg of syngeneic C3H/Sed mice was performed under a dissecting (x8) microscope. Local and radical resection achieved 20% (5/25) and 48% (12/25) tumor control, respectively. TCD80s (average dose expected to control 80% of irradiated tumors) for radiation alone given as one fraction per day for 5 consecutive days were 73.1 and 118.0 Gy for the microscopic and 8-mm tumors, respectively. Radiation therapy started at 4 or 7 days following local or radical resection enhanced both the local tumor control and the treatment-related morbidity represented by leg shortening. From enhancement ratios (ERs) for tumor control (TCD80 for radiation alone/TCD80 for postoperative radiation) and for leg shortening (dose for 5-mm leg shortening for radiation alone/postoperative radiation) values, therapeutic gain factors (TGFs) were derived as ER tumor/ER leg shortening. These were 1.3 and 1.4 for local and radical resection followed by radiation started on the 7th postoperative day, respectively. Corresponding figures for radiation started on the 4th postoperative day resulted in 1.2 for both resection procedures.


Secondary penile malignancies: the spectrum of presentation. Secondary penile carcinoma is a rare disease with signs and symptoms covering a wide spectrum, from simple erythema to priapism. We report two cases of penile metastatic involvement that are illustrative of this spectrum.


Malignant melanoma in a child with oculocutaneous albinism. Malignant melanoma is extremely rare in patients with albinism. To date, in the English language literature, there have been only sixteen documented cases of malignant melanoma in albino patients. These cases include thirteen cutaneous, one oral, one ocular, and one anal; only one of these was in a child. Here, we present the case of the youngest known albino patient to have cutaneous malignant melanoma.


Poorly differentiated solid type adenocarcinomas in the stomach: a clinicopathologic study of 71 cases. A review of 71 cases of solid carcinoma of the stomach selected from 2,738 cases of surgically resected poorly differentiated adenocarcinomas (PDAs) was undertaken. The average age of the patients, which included 47 men and 24 women, was 62 years. The clinicopathologic features of solid carcinomas were similar to those of the differentiated type adenocarcinomas. The solid carcinomas were divided into 42 of the solid alveolar type and 29 of the free-cell type; 32 of the former (76%) had foci of overt differentiated areas, while most of the latter type lacked such foci and had some signet-ring cells. Many tumors of both types had a prominent venous permeation and lymph node metastasis even in the early stage of invasion. The 5-year survival rates were 37% in all cases, 44% in cases with carcinoma with a limited invasion of the submucosa or the muscularis propria, and 27% in carcinoma invading down to the subserosa. These survival rates were poor in comparison with the 110 cases of ordinary PDA (diffuse type of Laurén) selected as controls. These findings suggest that tumors of the solid alveolar type are transformed from the differentiated type of adenocarcinoma, while those of the free-cell type are originally from PDAs. It is also suggested that solid carcinomas did show a high incidence of venous permeation and lymph node metastasis and that the prognosis for of venous permeation and lymph node metastasis and that the prognosis for this type of carcinoma is poor.


Inferior vena cava leiomyosarcoma.

Inferior vena cava leiomyosarcoma. Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M.D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy.


Surgical treatment for thoracic esophageal carcinoma in patients after gastrectomy. The clinicopathologic factors in 50 gastrectomized and 831 nongastrectomized patients with thoracic esophageal carcinoma were compared. The differences in various factors were not statistically significant except for the average duration of operation, which suggests that the association of esophageal carcinoma and previous gastrectomy is a chance finding. Thirty-four gastrectomized patients underwent abdominal lymphadenectomy and 16 did not. The postoperative survival curves for the two groups did not differ. In comparing the clinicopathologic factors between the two groups, only the tumor location differed significantly (P < .05). Nine patients (26.5%) with lesions in the mid- or lower thoracic esophagus in the gastrectomized group had positive nodes in the abdomen; the 5-year survival rate was 39.4%. Among them, 8 had gastrectomy for peptic ulcer. Abdominal lymphadenectomy is recommended for those patients with mid- or lower thoracic esophageal carcinoma who have had previous gastrectomy without lymphadenectomy.


Use of the Carpentier-Edwards porcine bioprosthesis: assessment of a patient selection policy. The Carpentier-Edwards bioprosthesis was implanted in 369 patients (414 valves) between May 1977 and December 1987 (age 67.2 +/- 0.5 years); 242 had aortic valve replacement, 80 had mitral valve replacement, 44 had multiple valve replacement, of which 41 were aortic and mitral valve replacement, 2 had isolated tricuspid valve replacement, and 1 had a pulmonary valve replacement. The selection criteria were the following: shorter life expectancy (253 patients) or contraindications to anticoagulants for organic (113 patients) or psychologic (38 patients) reasons, or both. The early mortality rate was 11.1% (aortic valve replacement, 9.1%; mitral valve replacement, 12.4%; aortic and mitral valve replacement, 23.1%). Total cumulative follow-up was 1456 pt-yr (mean 4.4 years, range 1 to 148 months), and the patient evaluation was 99.5% complete. Late mortality was 4.9%/pt-yr. Five-year survival was 70.4% +/- 2.7% overall, 74.3% +/- 3.2% after aortic valve replacement, 60.9% +/- 6.2% after mitral valve replacement (p < 0.03), and 60.7% +/- 8.1% after aortic and mitral valve replacement. Eight patients were reoperated on for primary tissue failure, and freedom from reoperation for structural valve deterioration was 97.5% +/- 1.2% at 5 years and 95.6% +/- 1.8% at 8 years. Failing aortic bioprostheses were explanted in four patients (0.4%/pt-yr) and mitral bioprostheses in seven (1.6%/pt-yr). No patient whose valve was inserted after the age of 70 had to be reoperated on for structural valve dysfunction. The probability of freedom from thromboembolism after 5 and 8 years of follow-up was 93.1% +/- 1.6% and 92.2% +/- 1.8%, respectively. The prevalence of anticoagulant-related hemorrhage was 0.8%/pt-yr (major 0.6%, minor 0.2%). Anticoagulants had to be maintained in 16.3% of the patients: 5.9% after aortic valve replacement, 35.7% after mitral valve replacement, and 45.8% after aortic and mitral valve replacement, while 80.0% were on a regimen of antiplatelet drug therapy. Prosthetic valve endocarditis happened in five patients (0.3%/pt-yr). Freedom from all valve-related morbidity and mortality, including hospital deaths, was 71.0% +/- 2.7% at 5 years and 58.6% +/- 4.6% at 8 years and was significantly better in the aortic valve replacement group (61.3% +/- 6.6% at 8 years) compared with the mitral valve replacement group (54.4% +/- 7.7% at 8 years; p = 0.04). This study confirms the satisfactory performance of the Carpentier-Edwards valve after aortic valve replacement in elderly patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Hemodynamic evaluation of the Monostrut and spherical disc Björk-Shiley aortic valve prosthesis with Doppler echocardiography. A Doppler echocardiographic study was performed to assess whether the Monostrut model of the Björk-Shiley valve (Shiley, Inc., Irvine, Calif.) had an improved hemodynamic performance in comparison with the spherical disc model in the aortic position. Twenty retrospectively randomly selected patients were studied, 10 with each valve type. Within each valve type two sizes of valve were studied, 21 and 23 mm. The two groups were comparable with respect to age, postoperative time, fractional shortening, New York Heart Association functional class preoperatively, and body surface area. Pulsed and continuous wave Doppler measurements were recorded at rest. Continuous wave Doppler recordings were performed every 2 minutes after exercise with supine bicycle ergometry until 10 minutes after exercise. Peak and mean gradients across the aortic valve prostheses were estimated. Both groups achieved a significant and comparable rise in heart rate with exercise. The mean gradients +/- standard error of the mean at rest and 2 minutes after exercise were 19.7 +/- 1.9 mm Hg and 30.9 +/- 2.2 mm Hg, respectively in the spherical disc group compared with 14.9 +/- 1.1 mm Hg and 23.6 +/- 1.7 mm Hg in the Monostrut group (p < 0.05 and p < 0.025, respectively). Peak transvalvular gradient at rest was 30.7 +/- 2.7 mm Hg in the spherical group compared with 23.9 +/- 1.9 mm Hg in the Monostrut group (p < 0.05). We conclude that the Monostrut Björk-Shiley valve prosthesis has better hemodynamic performance than the spherical disc model in the aortic position.