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The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors. Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test. A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival(P = 0.002 and P = 0.004, respectively). This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates., NA

Cyclosporine immunosuppression remains vital for successful lung transplantation. Cyclosporine also functions as a membrane active biological response modifier and has been noted to have a variable effect on ischemia-reperfusion (I/R) injury in various tissues. Glutathione plays an important role in the endogenous antioxidant defense system; plasma oxidized glutathione (GSSG) levels are useful as a sensitive indicator of in vivo oxidant stress and I/R injury. Lung transplantation results in ischemia, followed by a period of reperfusion, potentially producing functional injury. This study was designed to evaluate the effect of cyclosporine on oxygen radical generation in a model of single-lung transplantation. Single-lung transplantation was performed in 12 mongrel puppies, with animals assigned to receive either intravenous or aerosolized cyclosporine. Arterial blood and bronchoalveolar lavage fluid (BALF) samples were obtained to determine GSSG levels via a spectrophotometric technique. Samples were obtained both prior to and following the revascularization of the transplanted lung. Whole blood and tissue cyclosporine levels were determined via an high-performance liquid chromatography technique 3 hr following the completion of the transplant. Aerosolized cyclosporine administration resulted in greatly decreased arterial plasma and BALF GSSG levels, whole blood cyclosporine levels, and equivalent tissue cyclosporine levels when compared to intravenous cyclosporine delivery. These findings support the hypothesis that the transplanted lung is a source of GSSG production and release into plasma. Additionally, these findings suggest that cyclosporine may have a direct antioxidant effect on pulmonary tissue, with this activity occuring at the epithelial surface, an area susceptible to oxidant injury.

The human PCK1 gene encoding phosphoenolpyruvate carboxykinase (GTP) (PEPCK) was isolated and sequenced. There is 91% amino acid sequence identity (567/622 residues) between the human and the rat proteins, with conservation of intron/exon borders. A polymorphic dinucleotide microsatellite with the structure (CA)16(TA)5(CA) was identified in the 3' untranslated region of the cloned human PCK1 gene. This highly informative genetic marker has an estimated PIC value of 0.79 and heterozygosity of 0.81. Analysis of the RW pedigree demonstrated recombination between PCK1 and the MODY gene on chromosome 20. Multipoint linkage analysis of the reference pedigrees of the Centre d'Etude du Polymorphisme Humain localized PCK1 on the genetic map of chromosome 20 at a position distal to markers that are closely linked to MODY. PCK1 is part of a conserved linkage group on mouse Chromosome 2 with identical gene order but expanded length in the human genome.

It was the intent of this study to document, in general, the patterns and complications of heparin and protamine usage during carotid endarterectomy, aortic and femoral-popliteal-tibial reconstructions for occlusive disease, elective and emergent abdominal aortic aneurysmectomy, thromboembolectomy, and dialysis arteriovenous (AV) fistula placement by surgeons from North America and Europe. All vascular surgeons from the Society for Vascular Surgery (SVS) and the European Society for Vascular Surgery (ESVS) were surveyed by a voluntary, self-reported questionnaire. Six hundred and forty-six completed questionnaires (284 from SVS and 362 from ESVS), representing a 62% response rate, were returned for evaluation. Systemic and regional administration of heparin was common during vascular procedures performed by both SVS and ESVS surgeons. Use of protamine to reverse heparin anticoagulation varied among SVS and ESVS surgeons, respectively, during: carotid endarterectomy (54% vs. 26%, p p p p < 0.001). Adverse reactions to protamine among the 25 219 and 12 902 cases reported from SVS and ESVS surgeons, respectively, included: hypotension (1209 and 495 cases), pulmonary artery hypertension (65 and eight cases), anaphylaxis (52 and 10 cases), and death (seven and two cases). These adverse responses accounted for 5.3% and 4.0% of the SVS and ESVS cases, respectively. Although this study is subject to the known limitations of a retrospective survey, it is clear that heparin use is common. Protamine reversal of heparin anticoagulation is more common in North America. Severe reactions to protamine occur often enough to support the tenet that a safer compound is needed for heparin anticoagulation reversal.

Meckel's diverticulum is one of the primary concerns in the differential diagnosis of the pediatric patient with massive, acute gastrointestinal bleeding, intussusception, or abdominal pain of uncertain cause. The hospital course of two children with Meckel's diverticulum, successfully treated by laparoscopic excision, is presented, along with details of the operative procedure. Both patients recovered from the procedure without incident and were discharged at 24 and 48 hours after surgery. The authors believe a laparoscopic approach is safe and effective in the diagnosis and treatment of Meckel's diverticulum.

This study examines the hypothesis that whole gut irrigation with polyethylene glycol-electrolyte gavage solution (PEG-ELS) increases intravascular volume. Seventeen patients drank 6 to 8 liters of PEG-ELS in preparation for elective colonoscopy. The patients were weighed and serum electrolytes, albumin, hematocrit, blood urea nitrogen, and creatinine were obtained prior to the gavage and 8 hr following gavage. Plasma volume was measured before and after gavage using an isotope dilution technique involving 125 I-human serum albumin. No patients developed symptoms of intravascular volume excess or depletion following gavage. There was no significant change in body weight, serum sodium, chloride, potassium, bicarbonate, blood urea nitrogen, or creatinine following gavage with PEG-ELS. When measured by the isotope dilution technique, the mean plasma volume increased from 3174 +/- 117 ml before gavage to 3365 +/- 160 ml following gavage (P = 0.03). This represented a mean percentage change in plasma volume of 5.86 +/- 2.4 %. The percentage change in plasma volume associated with gavage ranged from -9.8 to +29.8%. This data supports the hypothesis that gavage with polyethylene glycol-electrolyte solution is associated with an increase in plasma volume. Although in most patients the increase in plasma volume is minimal, there is significant variability in this response, with some patients experiencing substantial increases in plasma volume.

Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood. The objective of this investigation was to assess the effectiveness of three methods of heparin administration. Heparin sulfate (75 IU/kg) administered to patients undergoing aortoiliac surgery was randomised to one of three methods: Group I (n = 9) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping; Group II (n = 9) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping; and Group III (n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping. Blood samples were analysed for anticoagulant activity from both the upper and lower extremities at 5, 15, 30, 60, and 120 minutes after heparin administration. Anticoagulation, as measured by aPTT, antifactor Xa levels, and ACT, was achieved in all three groups by 5 minutes, but initially with lower heparin activity (measured as antifactor Xa) in the upper extremity (Group II) and lower extremity (Group III), respectively. These differences were also evident in ACT and aPTT determinations. Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation (anti-factor Xa ~ 1 U/ml) in both upper and lower extremities after 5 minutes. With regional administration, rapid heparin redistribution occurs, but it takes longer to achieve the same level of anticoagulation distant from the site of administration. Nevertheless, from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation.

Multiple organ failure (MOF) is known to follow systemic inflammatory mediator activation associated with intestinal ischemia--reperfusion injury. In particular, the pulmonary microvasculature appears to be susceptible to MOF-related injury. This study was designed to evaluate the hypothesis that non-cellular plasma factors associated with intestinal ischemia without reperfusion also mediate pulmonary endothelial cell injury. Male Sprague--Dawley rats had intestinal ischemia induced by microvascular clip occlusion of the superior mesenteric artery for 30, 60, 90, or 120 min. Following each period of ischemia, plasma samples were obtained from the portal vein. Time-matched sham-operated animals served as controls. Monolayers of cultured rat pulmonary artery endothelial cells were then incubated with the plasma samples and ATP levels determined using a luciferin--luciferase assay. A 51Cr-release assay using labeled endothelial cells was performed under identical conditions to assess cytotoxicity. Endothelial cell ATP levels were 1.99 +/- 0.23 x 10-11 mole/[mu]g DNA in sham preparations. After a 4-hr incubation in plasma from the 90 and 120 min ischemia groups, cellular ATP levels fell significantly to 1.07 +/- 0.23 x 10-11 mole/[mu]g DNA, respectively (P P = NS). All animals survived 24 hr in the sham, 30, and 60 min groups. However, survival was 40 and 0% in the 90 and 120 min groups, respectively (P in vitro data with in vivo survival.

ATP loss is a prominent feature of cellular injury induced by oxidants or ischemia. How reduction of cellular ATP levels contributes to lethal injury is still poorly understood. In this study we examined the ability of H2O2 to inhibit in a dose-dependent manner the extrusion of fluorescent organic anions from bovine pulmonary artery endothelial cells. Extrusion of fluorescent organic anions was inhibited by probenecid, suggesting an organic anion transporter was involved. In experiments in which ATP levels in endothelial cells were varied by treatment with different degrees of metabolic inhibition, it was determined that organic anion transport was ATP-dependent. H2O2-induced inhibition of organic anion transport correlated well with the oxidant's effect on cellular ATP levels. Thus H2O2-mediated inhibition of organic anion transport appears to be via depletion of ATP, a required substrate for the transport reaction. Inhibition of organic anion transport directly by probenecid or indirectly by metabolic inhibition with reduction of cellular ATP levels was correlated with similar reductions of short term viability. This supports the hypothesis that inhibition of organic anion transport after oxidant exposure or during ischemia results from depletion of ATP and may significantly contribute to cytotoxicity.

We did a retrospective case control study to examine the relationship between the risk of dying for Michigan motor vehicle crash (MVC) drivers and the type of county (rural/nonrural) of crash occurrence, while adjusting for crash characteristics, age, sex, and the medical resources in the county of crash occurrence. The 1987 Michigan Accident Census was used to obtain data regarding all MVC driver nonsurvivors (733) and a random sample of all surviving drivers (2,483). County of crash occurrence was defined as rural or nonrural. The crash characteristics analyzed were vehicle deformity, seat belt use, and drivability of the vehicle from the scene. Age and sex of the driver were also analyzed. Medical resource characteristics for the county of crash occurrence were measured as the number of resources per square mile for each of the following: ambulances, emergency medical technicians (EMT), acute care hospital beds, and operating rooms, surgeons and emergency physicians. Also considered were the number and level of emergency rooms in the county of crash occurrence along with the maximum level of prehospital care available (basic life support versus advanced life support) in a county. Before adjusting, the relative risk (RR) for rural MVC drivers dying, compared to their nonrural counterparts, was 1.96. Adjustment for crash characteristics, age, and sex (using logistic regression) decreased the RR to 1.51. An attempt to add medical resource variables to the model resulted in high correlation with the rural/nonrural variable, as well as with each other. This multi-collinearity prevented us from providing a simple explanation of the role of medical resource variables as predictors of survival. We conclude that almost 50% of excess rural MVC mortality, as measured by the RR, can be accounted for by difference in crash characteristics and age. Delineation of the role of medical resources will require further investigation.

Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia-reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia--reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation.

Prostacyclin release from endothelial cells in culture appears increased by the presence of plasma, but occurrence of a similar phenomenon in intact vessels has not been established. In the present investigation release of 6-keto-PGF1[alpha], the stable breakdown product of prostacyclin, was quantitated from canine veins perfused ex vivo for 15 minute periods, using three different perfusates: 1) Hank's balanced salt solution (HBSS), 2) 20% platelet poor plasma (PPP) derived from heparinized blood, in HBSS, and 3) 20% PPP in HBSS with added arachidonic acid (AA). No differences in initial 6-keto-PGF1[alpha] release existed among the three perfusates. However, PPP and PPP + AA solutions were associated with lesser declines in release, than occurred with HBSS alone, these differences being statistically significant after 60 min of perfusion (p<0.05). When PPP derived from heparinized and citrated blood rather than from only heparinized blood was used, there was a significantly lower release of prostacyclin (p<0.05). The latter may be due to citrate binding of calcium. These data indicate that autologous plasma does not alter initial prostacyclin release from freshly harvested canine veins, but that it weakens the decline in release usually following prolonged periods of perfusion.

The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma, and autosomal dominant inheritance, but is distinct in that MEN 2B patients have neuromas of the mucous membranes. MEN2A has been linked to RBP3, D10S5, FNRB, D10S15, and D10Z1 near the centromere of chromosome 10. We examined linkage between MEN2B and RFLPs on chromosome 10 in all available members in two or three generations of 14 kindreds. The centromere marker D10Z1 was linked to MEN2B with a peak lod score of 5.42 at [theta] = 0.02. One possible recombinant was observed between D10Z1 and MEN2B. Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on the long arm (band q11). The most likely gene order FNRB-D10Z1-MEN2B was 27 times more likely than MEN2B-FNRB-D10Z1 and times more likely than FNRB-MEN2B-D10Z1. Additional data will be required to establish the order of these loci with confidence.

In the anesthetized open-chest dog the ischemic area produced by coronary occlusion is surrounded by an area of nonischemic contractile dysfunction, identified as the functional border zone. To establish whether a similar functional border zone exists in the conscious animal during acute regional ischemia and to determine its spatial dimensions and temporal changes, we performed simultaneous two-dimensional echocardiography and radioactive microsphere studies in nine chronically instrumented dogs. We produced circumferential flow-function maps at 22.5-degree intervals over the full circumference of the left ventricle at the midpapillary muscle level during control conditions, 5 minutes after left circumflex occlusion, and 2.5 hours after left circumflex occlusion. After occlusion there was no change in left ventricular end-diastolic area, an increase in left ventricular end-systolic area (p p p p <0.01) in the functional border zone, there was no difference in subendocardial blood flow between the functional border zone and the control nonischemic area. We conclude that a discrete functional border zone exists in the conscious dog during acute regional ischemia produced by circumflex coronary occlusion, which does not change during the early evolution of myocardial infarction. The functional border zone likely contributes to minor overestimation of infarct size in the early hours after myocardial infarction if extent of left ventricular dysfunction is used as an index of infarction in humans.

Human milk galactosyltransferase (EC 2.4.1.22) was purified to homogeneity using affinity chromatography. Edman degradation was used to determine the amino acid sequences of eight peptide fragments isolated from the purified enzyme. A 60-mer "optimal" oligonucleotide probe that corresponded to the amino acid sequence of one of the galactosyltransferase peptide fragments was constructed and used to screen a [lambda]gt10 cDNA library. Two hybridization-positive recombinant phages, each with a 1.7 Kbp insert, were detected among 3 x 106 recombinant [lambda]gt10 phages. Sequencing of one of the cDNA inserts revealed a 783 bp galactosyltransferase coding sequence. The remainder of the sequence corresponded to the 3'-region of the mRNA downstream from the termination codon.

A recent clinical case afforded an opportunity to study the effects of duodenal stimulation on plasma human pancreatic polypeptide and gastrin concentrations, independent of gastric stimulation. A distension stimulus was provided by rapid injection of 100 ml of water and saline via a T-tube into an isolated duodenal afferent limb. In a third experiment, the saline contained 200 pg/ml of heptadeca-peptide human gastrin. Within 2 min after each injection, a rapid rise in circulating human pancreatic polypeptide levels appeared that fell promptly towards basal thereafter. Injections of 100 ml of Flexical, a supplemental tube feeding, resulted in a biphasic human pancreatic polypeptide response, the initial peak comparable to that seen following distension with water, saline, or saline containing gastrin, and a second peak of much greater magnitude and duration followed the initial peak. Plasma gastrin concentrations were not influenced following any of the stimuli. Duodenal distension alone may induce an early transient increase in plasma human pancreatic polypeptide concentrations, while intraduodenal nutrients per se may induce a later increment of greater magnitude and duration.

A thin-layer chromatographic method for bile acids has been described which separates glycine conjugates, taurine conjugates, and free bile acids into three separate bands. The solvent system used for this purpose is ethanol-isopropyl alcohol-isooctane-ethyl acetate (25:10:10:10). This method is time saving and very simple for quantitative estimation of the glycine:taurine ratio in biological specimens.

Although low molecular weight (LMW) dextran has been said to decrease the lethality of experimental acute pancreatitis (AP) by reversing stasis in the pancreatic microcirculation, the actual mechanism(s) of action is unknown. This investigation was designed to measure the effects of low molecular weight dextran on pancreatic capillary flow (QCAP) and arteriovenous shunt flow (QAVS), and on pancreatic oxygen consumption (O2CP) following bile-trypsin-induced AP in dogs. Total pancreatic blood flow (QT) was measured with an electromagnetic flow probe on the superior pancreaticoduodenal artery (SPDA). QAVS was measured by liver trapping of 99mTc-albumin microspheres after SPDA injection. QCAP was calculated as QT minus QAVS. Seventeen dogs were treated with lactated Ringer's (LR) solution at 6.5 ml/kg/hr; 10 dogs were treated with LMW dextran 10% in normal saline at 1.5 ml/kg/hr plus LR at 5.0 ml/kg/hr. Mean arterial and central venous pressures remained constant throughout the 4-hr experiment. In the dogs receiving LR only, QT decreased from 42.7 to 24.4 ml/min (P QAVS remained constant at 1.35 +/- 0.04 ml/min. During the first 30 min O2CP decreased from 1.17 to 0.76 ml O2/min (P QT and QCAP without altering QAVS. The decrease in O2CP in association with a constant QAVS suggests a metabolic block to oxygen uptake at the cellular level. Continuous infusion of LMW dextran at a dose of 1.5 ml/kg/hr in the dog does not reverse these abnormalities.

Researchers and practitioners have expressed considerable interest in contingency contracting as a promising intervention strategy for enlisting patient cooperation, particularly with regard to long-term treatment regimens. After brief examination of the theoretical background, the authors summarize advantages of contracting, describe elements essential to the development of a contract, and enumerate those ingredients in the contracting process thought to be critical for achieving optimal results. They review relevant research efforts in terms of their designs, methods, target and contracted health-related behaviors, contingencies employed, and initial and follow-up results. On the basis of this review, current issues regarding contingency contracting are raised, and practical considerations for large-scale application are noted along with recommendations for future research.

Von Recklinghausen neurofibromatosis (VRNF) is one of the most common inherited disorders affecting the human nervous system. VRNF is transmitted as an autosomal dominant defect with high penetrance but variable expressivity. The disorder is characterized clinically by hyperpigmented patches of skin (cafe au lait macules, axillary freckles) and by multiple tumors of peripheral nerve, spinal nerve roots, and brain (neurofibromas, optic gliomas). These tumors can cause disfigurement, paralysis, blindness, and death. We have determined the chromosomal location of the VRNF gene by genetic linkage analysis using DNA markers. The VRNF gene is genetically linked to the locus encoding nerve growth factor receptor, located on the long arm of chromosome 17 in the region 17q12-->17q22. However, crossovers with the VRNF locus suggest that a mutation in the nerve growth factor receptor gene itself is unlikely to be the fundamental defect responsible for the VRNF phenotype.

Intestinal absorption of d-xylose was studied during the postprandial period after ingestion of a provocative meat meal in experimental animals with chronic celiac and superior mesenteric artery occlusions. Statistically significant impairment of d-xylose absorption occurred in the presence of celiac artery occlusion. In theory this was attributed to the effect of collateral circulation upon blood flow velocity within the superior mesenteric artery and altered perfusion of its distal branches.

A fatal recurrence of a left atrial myxoma was observed despite resection of the original tumor complete with its stalk and a portion of atrial septum. The evidence suggests that this recurrent tumor developed from "pre-tumor" cells in the region of the fossa ovalis. The rate of growth of the second tumor was faster than would have been predicted. Clinical manifestations were similar to those with the initial tumor. Wide excision of the atrial septum with the stalk of such tumors should offer the best chance for operative cure, but prolonged postoperative observation is important if signs of recurrence are to be detected at a time when operative removal can be carried out with minimal risk to the patient.

Based on urinary studies of patients with pheochromocytoma as compared to hypertensives considered to be without this tumor, rigorous biochemical criteria for diagnosis are proposed. Free catecholamines in 90% and metanephrine metabolites in 100% of the pheochromocytoma patients' urine samples exceeded the normal (hypertensive) values by more than 5 SD. No patient without pheochromocytoma has falsely positive values in both free catecholamine and metanephrine metabolite determinations. No patient with a pheochromocytoma had a urine sample negative for metanephrine metabolites. The combination of these studies has given excellent accuracy for definitive diagnosis.

Intra-aortic balloon tamponade of the infra-diaphragmatic aortic is an effective means of reducing intra-abdominal hemorrhage. However, its therapeutic use when preceeded by hypotension and in the face of persistent hypovolemia, often results in death or hind limb paralysis in dogs.

A significant decrease in concentration of branched-chain amino acids in skeletal muscle of cirrhotic patients has been observed. These data are presented in further support of the concept that a relative deficiency of these amino acids may be present in cirrhotic patients.

Production of hematin from hemoglobin in vitro is augmented by a mixture of powdered pancreatic enzymes and human pancreatic juice. Those enzymes which most affected the rate of conversion of hemoglobin to hematin were lipase, elastase, and trypsin. These same enzymes were also most active in hematin production from red cells.

Traumatic dislocation of the testis is a rare event in which the full extent of the dislocation is present immediately following the initial trauma. We present a case in which the testicular dislocation progressed over a period of four days following the initial scrotal trauma.

ObjectiveGoldenhar syndrome (oculoauriculovertebral dysplasia) is associated with anomalies in multiple organ systems. Renal abnormalities have also been reported with the complex, but the incidence of associated genitourinary malformations has not been defined.MethodWe have reviewed our experience with 28 children with Goldenhar syndrome evaluated during the past twelve years. Twenty children underwent imaging evaluation of the urinary tract and 14 (70% of those imaged) children had urinary tract anomalies.ResultsThe majority of anomalies presented as an incidental finding on a screening ultrasound (8 patients) or during cardiac catheterization (2 patients). Two children presented with urinary tract infection, 1 child presented with renal failure, and another was diagnosed antenatally. The genitourinary anomalies included the following: ectopic and/or fused kidneys (8 patients), renal agenesis (7), vesicoureteral reflux (5), ureteropelvic junction obstruction (2), ureteral duplication (2), and multicystic kidney (1 patient). Four children have undergone surgical intervention.ConclusionOur experience in children with Goldenhar syndrome suggests that the incidence of genitourinary anomalies is higher than previously reported. A screening ultrasound in the neonatal period allows for early intervention in those children with significant urologic abnormalities.

Determination of contact areas in diarthrodial joints is necessary for understanding the state of stress within the articular cartilage layers and the supporting bony structures. The present study describes the use of a stereophotogrammetry (SPG) system [Huiskes et al., J. Biomechanics,18, 559-570 (1985) and Ateshian et al., J. Biomechanics, 24, 761-776 (1991)] for determining contact areas in diarthrodial joints, using a surface proximity concept similar to the one used by Scherrer et al. [ASME J. biomech. Engng, 101, 271-278 (1979)]. This method consists of evaluating the proximity of the articular surfaces to determine joint contact areas using precise geometric models of the joint surfaces obtained from the SPG system, and precise kinematic data, also obtained from SPG. In this study, the SPG method for determining contact areas is compared to other commonly used methods such as dye staining, silicone rubber casting and Fuji film contact measurement techniques which have been often used and reported by other investigators. The bovine glenohumeral joint and the bovine lateral tibiofemoral articulation (without the meniscus) were used to represent congruent and incongruent joints, respectively. While all the methods yielded consistent contact patterns for the incongruent tibiofemoral articulations, the results for the congruent bovine glenohumeral joints showed that the SPG and Fuji film methods were in better agreement than those obtained from the dye staining and silicone rubber casting methods. The advantages of the new SPG method are that it can be used for intact joints, and used repeatedly and quickly thus making contact-area movement analyses possible [Soslowsky et al., J. orthop. Res., 10, 524-534 (1992)]. The results of this comparison study show that the SPG technique is a reliable and versatile method for determining contact areas in diarthrodial joints.

Norepinephrine (NE) is used clinically to increase oxygen delivery (DO2) by increasing cardiac output (CO). The rate of administration of NE is usually based on frequent measurements of blood pressure (BP) and infrequent measurements of CO with little regard for oxygen delivery or consumption dynamics. Although the ultimate goal of an inotropic drug is to increase DO2 in excess of metabolic requirements (VO2), the effect of NE on the DO2/VO2 ratio has not been previously studied. In the present investigation, healthy anesthetized dogs were infused with various doses of intravenous NE. These dosages were chosen to span the range used clinically. NE administration caused a significant primary increase in VO2 which was dose dependent (P 2 was observed (P 2 minimally exceeded the increase in VO2 at lower doses of NE and the relative increase in VO2 exceeded the change in DO2 at a dose of 0.04 [mu]g/kg/min. Minimal advantage to oxygen utilization physiology at low doses of NE and a potential deleterious effect at a dose of 0.04 [mu]g/kg/min were observed, therefore, despite associated increases in mean systemic blood pressure. The effectiveness of NE administration could be most effectively monitored by the mixed venous oxygen saturation (SVO2), rather than by intermittent assessment of BP, CO, or DO2. Even though values for SVO2 and CO do track closely for the dose of drug administered, SVO2 is a more accurate summation of all components of oxygen consumption and delivery and can be easily and continuously monitored.

Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli [beta]-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. Multiple analyses (including immunohistochemistry, histochemistry, transmission electron microscopy, RNA in situ hybridization, nucleotide pool analysis, and enzyme assay) confirmed efficient expression of [beta]-galactosidase and rat HPRT. Transgene expression was evident in both neurons and glia. Clinically, no evidence of meningitis or cerebritis was observed and no focal neurological deficits were detected in the animal. These preliminary studies indicate that recombinant adenovirus is capable of mediating high level transgene expression to the brains of higher order mammals.

We report the isolation of a gene encoding a novel member of the family of melanocortin receptors. The mouse melanocortin-5 receptor (mMC5R) responds to melanocortins with an increase in intracellular cyclic 3', 5'-adenosine monophosphate (cAMP) concentrations. Stimulation of the mMC5R by the melanocortins revealed a hierarchy of potency in which [alpha]-melanocyte stimulating hormone ([alpha]-MSH)> [beta]-melanocyte stimulating hormone ([beta]-MSH)> adrenocorticotropic hormone (ACTH)> [gamma]-melanocyte stimulating hormone ([gamma]-MSH). Further structure-activity studies indicated that amino- and carboxyl-terminal portions of [alpha]-MSH appear to be key determinants in the activation of mMC5R whereas the melanocortin core heptapeptide sequence is devoid of pharmacological activity. Northern blot analysis demonstrated the expression of mMC5R mRNA in mouse skeletal muscle, lung, spleen, and brain.

Endothelin-mediated vasoconstriction may theoretically aggravate ischemic neuronal damage. Although investigators have demonstrated that endothelins are produced by cerebral microvessel endothelial cells, astrocytes and neurons in vitro, whether endothelins are produced during cerebral ischemia is still unclear. The purpose of this study, therefore, was to measure endothelin-1 in brain tissue and plasma following middle cerebral artery occlusion and to examine the relationship between brain tissue and plasma endothelin-1 levels. The middle cerebral artery of rabbits was occluded for 2, 4 or 24 h. The amount of endothelin-1 in both brain tissue and plasma was determined by RIA. The results demonstrate that the concentrations of endothelin-1 in the ischemic brain tissue and plasma are both significantly increased after focal cerebral ischemia (P <0.01). The data confirm that an acute and marked increase of endothelin-1 in brain tissue and plasma is associated with focal ischemic events. The possibility that endothelin-1 has a role in neuronal cell damage following focal ischemia warrants further attention.

We sought to determine whether a contaminated open fracture was a reliable component for calculating the Outcome Predictive Score in patients with multiple injuries. We studied 41 patients whose primary source of contamination was open extremity fractures. Only one of the 41 patients developed osteomyelitis. The rate of infection from an open fracture is minimal in the multiply injured patient. Inclusion of patients with open fractures in studies that assess the likelihood of infection and the value of anti-infective agents incorrectly identified patients for clinical trials and results in an overestimation of survival based on the Outcome Predictive Score. These findings suggest that open fractures should be excluded as an entry criterion in future clinical trials.

Substernal goiter remains a common consideration in the differential diagnosis of a mediastinal mass. Given the potential for serious goiter-related complications as well as the inability to rule out associated malignancy, it has been our policy to treat all substernal goiters surgically over the past 20 years. During the period from 1972 to 1992, 101 patients with the major component of their goiters below the thoracic inlet underwent thyroidectomy. The most common symptoms were related to airway compression (82%) and dysphagia (37%). In addition, there was a 13% incidence of malignancy and a similar occurrence of thyrotoxicosis in this group of patients. Although total thyroidectomy was performed only for malignant goiters during the first decade, 71% of patients had total thyroidectomies during the second and, with a few exceptions, all procedures were done through a cervical incision. No patient developed permanent hypoparathyroidism, although two developed permanent unilateral vocal cord palsies. Surgical treatment is a safe procedure with rare mortality (none in this series) and low morbidity. Total thyroidectomy was not associated with added morbidity and it eliminates the possibility of recurrent goiter.

A total of 7 patients with high grade, T3a (Stage B2) bladder cancer were treated with external radiation therapy and interstitial iridium implantation from May 1986 through March 1988. Follow-up has ranged from nineteen to sixty-one months with a median of forty months. One patient has required a cystectomy and is currently free of disease, and 1 patient has had recurrence of his cancer and metastatic carcinoma has developed; 5 are free of disease and have maintained their usual state of bladder function. Iridium implantation maintains bladder function and is effective therapy for selected individuals with localized, muscle-invading bladder cancer.

Pulmonary artery (PA) mixed venous saturation (SO2) has become a crucial monitor in the adult intensive care unit, but is not used in neonates because of the difficulty in PA catheterization. We evaluated the possibility of utilizing the right atrial venous oxygen saturation (RAO2), which is easily accessed in the neonate, as a monitor of the effects of mechanical ventilation and intravascular volume in an animal model selected to be the size of the human neonate. A continuous RAO2 monitoring catheter was placed into the right atrium of 16 normal rabbits (2.2 to 4.1 kg). Oxygen delivery was manipulated by alterations in peak inspiratory pressure (PIP) (n = 6), positive end-expiratory pressure (PEEP) (n = 6), or by progressive hypovolemia (n = 4). RAO2 decreased with onset of mechanical ventilation alone from 69% +/- 6% to 61% +/- 5% (P 2O, the RAO2 progressively decreased from 59% +/- 4% to 49% +/- 6% (P 2O, the RAO2 progressively decreased from 64% +/- 5% to 33% +/- 16% (P 2 approached baseline after return to continuous positive airway pressure (CPAP) of 3 cm H2O. Progressive phlebotomy to a total of 10 mL/kg resulted in a decrease in RAO2 from 70% +/- 6% to 27% +/- 5% (P 2 to near baseline. Peripheral arterial oxygen saturation remained at a constant 100% throughout each protocol. With oxygen consumption stable, the RAO2 is an excellent monitor of the effect of airway pressure or of hypovolemia on oxygen delivery. Use of the peripheral arterial oxygen saturation alone as a parameter for monitoring ventilator or intravascular volume effect is not adequate. RAO2 monitoring may be a powerful tool in the management of the critically ill neonates.

The ability of bombesin to stimulate acetylcholine release from guinea pig myenteric plexus neurons was studied using a primary neuronal culture system. Bombesin caused dose-dependent increases in [3H]acetylcholine (ACh) release from guinea pig myenteric plexus neurons. ACh release in response to 0.5 mM bombesin (160 +/- 12% of control) was blocked by exposure to a calcium-free medium (116 +/- 13%) by nifedipine (101 +/- 11%) and by omega conotoxin (107 +/- 10%). Bombesin-stimulated ACh release was inhibited the protein kinase C inhibitor, H7, but was not affected by inhibitors of the cAMP signaling pathway. Interactions with inhibitory neuropeptides was implied by sensitivity of bombesin-stimulated ACh release to neuropeptide Y and galanin. The findings suggest that bombesin activation of protein kinase C in myenteric neurons resuits in increased acetylcholine release.

We report on 2 patients, one female and one male transsexual; in both, Type III stress urinary incontinence developed after gender reassignment surgery. Both patients were treated by periurethral injection of gluteraldehyde cross-linked collagen resulting in a marked symptomatic improvement in association with a significant rise in abdominal leak point pressures. We believe these are the first reported cases of collagen injection being used for urinary incontinence after gender reassignment surgery.

Acute obstruction of a patent processus vaginalis occurred in two boys, mimicking incarceration of an inguinal hernia. In fact, obstruction was caused by an intussusception of the processus vaginalis forming an intussuscipiens that occluded the hernia sac. This lesion, described previously in 1896 and in 1974, is one of the mechanisms by which an asymptomatic hernia or hydrocele becomes acutely symptomatic.

A strong association between HLA-DR2, DQ1 and narcolepsy-cataplexy has been known since 1986. In 1990 a subdivision (HLA-DR15, DQ6) was shown to be equally associated. Narcolepsy symptoms include rapid eye movement (REM)-sleep intrusion hallucinations during the day. Some narcoleptics may be so hallucinated that they become delusional and receive a diagnosis of schizophrenia. Fifty-six inpatient schizophrenics and 56 normal controls were compared to see if there was an excess of the narcolepsy-associated antigens (NAA) among schizophrenics. Patients had frequency of the NAA 3.89 times higher than controls. After a subset was studied by night (n = 9) and day (n = 7) polysomnography, two patients were found to be true narcoleptics. Their psychosis improved with treatment for narcolepsy. When NAA(+) and NAA( - ) schizophrenics were compared, the NAA(+) subgroup had significantly higher Brief Psychiatric Rating Scale (BPRS) scores and more hospitalizations. There were no effects attributable only to gender or race. We conclude that narcolepsy can simulate schizophrenia in some cases, and that even in nonnarcoleptic patients, the HLA-DR15, DQ6 antigens mark a group of severe schizophrenics that merits further study.

The growth of immunogenic tumours stimulates the generation of tumour-sensitized, but not functional, pre-effector T cells in the draining lymph nodes. These pre-effector cells can mature into effector cells upon in-vitro stimulation with anti-CD3 and IL-2. In the current study, using a defined, poorly immunogenic tumour, B16-BL6 melanoma, the pre-effector cell response was not evident during progressive tumour growth but was elicited by vaccination with irradiated tumour cells admixed with Corynebacterium parvum. After anti-CD3/IL-2 activation, these cells were capable of mediating the regression of established pulmonary metastases. The efficacy of the vaccine depended on the doses of both tumour cells and the adjuvant. While higher numbers of tumour cells were more effective, an optimal dose (12.5 [mu]g) of C. parvum was required. The dose of irradiation was not a critical factor. After vaccination, kinetic studies revealed that the pre-effector cell response was evident 4 days later and declined after 14 days. These observations illustrate the potential role of active immunization in the cellular therapy of cancer.

Recent studies have demonstrated that cardiac and skeletal myocytes share the ability to take up and stably express plasmid DNA injected directly into myocardium or skeletal muscle in vivo. Although this is a relatively inefficient process, with less than 1% of the myocytes expressing the injected recombinant DNA, expression in these cells is stable for periods of at least 6 months. The majority of the injected DNA is maintained in myocytes as an episome and apparently does not undergo DNA replication. The direct DNA injection approach has been used to map cardiac-specific transcriptional regulatory elements in cellular promoter/enhancers. Expression of recombinant proteins in the heart following direct DNA injection also holds promise for the treatment of a variety of acquired and inherited cardiovascular diseases.

A ten-year review of 198 patients with Stage D2 prostate cancer identified 13 patients (6.6%) who exhibited objective responses to hormonal treatment, as indicated by regression of a positive bone scan, CT scan, or chest x-ray film. Four patients had complete responses and 9 patients achieved partial responses as judged by the National Prostatic Cancer Project criteria. Median survival for those with objective treatment response has not yet been reached (>44 months) compared with twenty-four months for the nonresponders (p = 0.00006). Although relatively uncommon, objective treatment response in Stage D2 prostate cancer is correlated with an improved prognosis.