Citations

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

High-dose glucocorticoid treatment results in protein wasting. To determine whether such therapy affects leucine oxidation in the postabsorptive state and the disposal of dietary amino acids, eight normal subjects were studied twice in random order, once after 5 days of prednisone (20 mg three times daily) and on a second occasion without prednisone as a control. In the postabsorptive state prednisone therapy increased (P less than 0.05) plasma concentrations of leucine, alpha-ketoisocaproate, glucose, insulin, and C-peptide, as well as leucine carbon flux and oxidation calculated by means of isotope dilution techniques and [1-13C]leucine. During infusion of a chemically defined meal, total leucine carbon flux and oxidation increased similarly on both study days, but leucine oxidation was greater (P less than 0.01) during prednisone treatment; net leucine balance became positive on the control day but remained negative or zero on the prednisone study day despite higher (P less than 0.05) plasma insulin concentrations. These studies demonstrate that high-dose glucocorticoid treatment impairs the balance of the essential amino acid leucine in both the postabsorptive and absorptive states in humans.

Eight hundred fifty-seven determinations of the pH of venous blood with simultaneous blood pressure observations were carried out on 590 patients. The pH of venous blood of the patients who had been under medication for a long period before the tests did not vary significantly from that of patients who had had no medication. The most consistent result was the rise in the pH of venous blood 30 minutes after a dose of phentolamine hydrochloride (Regitine). The oral administration of 40 grains of sodium bicarbonate did not increase the response of the blood pressure during the histamine test, irrespective of the type of previous medication, even though the pH of the venous blood was low initially and rose to normal levels after the administration of the sodium bicarbonate. This may be due to the fact that none of the patients had pheochromocytomas with excessive release of pressor amines.

Abstract Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers. Experimental Design: This was a randomized, double-blind, placebo-controlled, phase II study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab. Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (HR, 1.13; 95% confidence interval, 0.76–1.67; P = 0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs. the placebo group, respectively) were fatigue (53.7% vs. 47.5%), nausea (39.0% vs. 35.0%), decreased appetite (34.1% vs. 27.5%), and constipation (28.0% vs. 32.5%). The most common grade 3/4 TEAE in the ontuxizumab group versus placebo was back pain (11.0% vs. 0%). No single biomarker clearly identified patients responsive to ontuxizumab. Conclusions: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated. Clin Cancer Res; 24(2); 316–25. ©2017 AACR.

Abstract Background While several studies have identified risk factors for PJI using insurance claims data, these data sets have been limited to a single regional insurance dataset or to the Medicare population. We sought to investigate risk factors for early PJI among patients undergoing total hip or knee arthroplasty (THKA). Methods All patients who underwent primary THKA between January 1, 2004 and July 31, 2014 with 12 months of continuous preceding medical and pharmacy insurance coverage were included in the study. The primary outcome of PJI required both a compatible procedure code and a diagnostic code during an inpatient stay from the time of THKA through 90 days after discharge. Comorbidities were based on ICD-9 codes in the preceding 12 months and patients with a prior diagnosis of PJI during that time period were excluded. Univariate and multivariate analysis was performed using logistic regression. Results A total of 147,053 patients underwent THKA during the study period, including 97,448 patients with TKA and 49,605 with THA. PJI occurred in 754 (0.5%) patients. Female gender was independently associated with lower odds of PJI (Figure). A number of biologically plausible factors were associated with increased risk, including chronic skin ulcer, obesity, substance use disorders, joint sarcoma, and malnutrition. The adjusted odds of PJI increased in a stepwise fashion with each increase in the Charlson comorbidity index (CCI), with those with a score of 4 or more having a nearly 2-fold adjusted odds of PJI compared with a score of 0 (OR 1.91; 95% CI 1.29 −2.82). Previously observed risk factors diabetes mellitus, rheumatoid arthritis, and chronic renal failure were associated with increased odds of PJI on univariate analysis, but not after adjustment. Conclusion These data identify several potentially modifiable risk factors for preoperative optimization, including obesity, malnutrition, chronic skin ulcers, and substance-use disorders. The level of comorbidity as assessed by the CCI provides a rough estimate of the increasing risk of PJI. The pathobiology of additional risk factors observed here deserves further study. Disclosures All authors: No reported disclosures.

Background: The first description of the voluntary motor function of the facial nerve and separate sensory-motor contributions of the trigeminal nerve is most commonly attributed to Charles Bell. However, a review of the original scientific accounts and subsequent historical publications question the validity of this credit. The objective of the present historical analysis is to clarify the contributions of Herbert Mayo toward discovering the functions of the fifth and seventh cranial nerves and to raise awareness of this historical controversy within the medical literature. Methods: Review of Charles Bell's and Herbert Mayo's original dissertations published between 1821 and 1823, and subsequent reports relevant to these primary works. Results: Bell's submissions to the Royal Society of London in 1821 and 1822 describe the seventh nerve as the “respiratory nerve of the face” responsible for involuntary coordination of facial movement with the organs of respiration. Separately, Bell states that the fifth nerve is responsible for sensibility and voluntary movement of the facial muscles. In these accounts, Bell only peripherally alludes to the motor function of the seventh nerve and often comments inaccurately on fifth and seventh cranial nerve innervation. In contrast, in 1822 and 1823, Herbert Mayo first accurately and unequivocally defined the voluntary motor function of the facial nerve and sensory-motor function of the trigeminal nerve on the basis of his detailed experiments. The ultimate transfer of acknowledgment to Bell was rooted in surreptitious reworking of Bell's original dissertations and personal attacks against Mayo rather than arguments of scientific merit. Conclusion: Several notable clinicians and anatomists have contributed to our current understanding of the anatomy and physiology of the facial and trigeminal nerves, including Charles Bell; however, Herbert Mayo should be remembered for first providing a more accurate and clear description of their separate functions.