STUDIES ON EXPERIMENTAL PNEUMONIA : IX. PRODUCTION IN MONKEYS OF AN ACUTE RESPIRATORY DISEASE RESEMBLING INFLUENZA BY INOCULATION WITH BACILLUS INFLUENZ?.

Twelve normal monkeys inoculated on the mucous membranes of the nose or nose and mouth with a strain of Bacillus influenzæ; originally isolated in pure culture from the pleural exudate of a case of empyema following influenzal pneumonia in man and subsequently raised in virulence by animal passage, developed an acute self-limited respiratory disease of from 3 to 5 days duration, characterized by sudden onset with profound prostration, the development of rhinitis and tracheobronchitis, with sneezing, cough, and the outpouring of a scanty mucoid, or mucopurulent exudate, a variable febrile reaction, and either a leucopenia or no significant change in the leucocyte count. This disease was complicated in five instances by purulent sinusitis of one or both antra, in three by bronchopneumonia. Bacillus influenzæ was recovered at autopsy from the lesions of the disease either in pure culture or in association with organisms that are normal inhabitants of the upper respiratory tract of monkeys. Of ten normal monkeys injected intratracheally with the same strain of Bacillus influenzæ, seven developed bronchopneumonia, two developed tracheobronchitis without pneumonia, and one resisted infection. The general symptoms and duration of the disease were similar to those of the preceding group. There were a severe cough and accelerated respirations. Bacillus influenzæ was recovered in pure culture from the lungs, bronchi, or trachea in the animals killed during the active stage of the disease. It disappeared promptly from the respiratory tract with recovery. The significance of the first series of experiments in which monkeys were inoculated in the upper respiratory tract is twofold. First, they establish the fact that Bacillus influenzæ can initiate in monkeys an acute infection of the normal mucous membranes of the upper respiratory tract; that is, it can act as a primary incitant of respiratory infection without the assistance of a preceding or concomitant contributing cause. In this respect it differs radically from the pneumococcus and Streptococcus hæmolyticus, since experiments previously reported^{2, 4} have shown that neither of these organisms possesses the property of initiating an infection of the normal mucous membranes of the upper respiratory tract of monkeys, even though the strains used were incalculably more virulent for monkeys than the strain of Bacillus influenzæ used in the foregoing experiments. Secondly, the experiments show that Bacillus influenzæ infection of the mucous membranes of the upper respiratory tract may spread by continuity to the paranasal sinuses, setting up an acute sinusitis, that it spreads readily to the lower respiratory tract, producing a tracheobronchitis and permitting the ready invasion of secondary bacteria, and that it may penetrate as far as the terminal bronchioles, alveolar ducts, atria, and alveoli, there setting up a bronchiolitis and true bronchopneumonia. In these respects it likewise differs radically from the pneumococcus and Streptococcus hæmolyticus which do not possess these pathogenic properties as previous experiments have shown.^{2, 4} The bearing of these facts on the possible etiologic relation of Bacillus influenzæ to influenza is important, since they show that Bacillus influenzæ possesses certain definite primary pathogenic properties which distinguish it and therefore separate it from the group of recognized secondary organisms in influenzal complications, of which the pneumococcus and the streptococcus are the most frequent. The possible etiologic relation of Bacillus influenzæ to influenza is further supported by the character of the respiratory disease that occurred in the monkeys. The sudden onset with profound prostration, the absence of leucocytosis or often a leucopenia, the congestion of the mucous membranes of the respiratory tract, the development on the 2nd or 3rd day of an irritative cough due to an inflammatory tracheitis or tracheobronchitis, the brief self-limited course of the infection, and the irregular febrile reactions are all characteristic of influenza. Many of these symptoms were in striking contrast with the symptoms and course of pneumococcus or streptococcus infections in monkeys in which there were no prostration at onset, invariable leucocytosis, and infrequent cough developing only late in the disease. While all the above features of the disease produced in monkeys are characteristic of influenza in man, none are pathognomonic and, in fact, it is doubtful whether uncomplicated influenza possesses any pathognomonic features by which it may be diagnosed certainly in the absence of an epidemic. Even during epidemic times many respiratory infections arise which, though presumably influenza, it is impossible to diagnose as such with certainty. Nor does pathology help in this respect, since there would appear to be no established distinctive lesions of uncomplicated influenza in man, nor for that matter of the complications of influenza, apart from the complications which have been ascribed by Pfeiffer,⁵ MacCallum,⁶ Wolbach,⁷ and others to infection with Bacillus influenzæ because of the association of Bacillus influenzæ in pure culture with these complications. For these reasons, although the disease produced in monkeys appears to be essentially identical with influenza in man with respect to its clinical course and complications, it is impossible to determine certainly whether it is actually so. The experiments are advanced, therefore, as evidence in favor of the etiologic relation of Bacillus influenzæ to influenza, though they do not permit of a definite conclusion in this respect. Their bearing upon the relation of Bacillus influenzæ to certain of the complications of influenza would appear to be reasonably conclusive. The recovery of Bacillus influenzæ in pure culture at autopsy from the antra, from the trachea and bronchi, and from the lungs in some of the animals developing sinusitis, bronchiolitis, and a characteristic type of bronchopneumonia confirms by animal experiment the etiologic relation of Bacillus influenzæ to these complications of influenza, which hitherto has rested solely upon the frequent association of the influenza bacillus with these lesions in man. The production of tracheobronchitis and the same type of bronchopneumonia by the intratracheal injection of Bacillus influenzæ in the second series of experiments serves as additional confirmation of this, but has no direct bearing on the etiologic relation of Bacillus influenzæ to uncomplicated influenzæ.     

Quantification in Patient Urine Samples of Felbamate and Three Metabolites: Acid Carbamate and Two Mercapturic Acids

PURPOSE: Previously we proposed and provided evidence for the metabolic pathway of felbamate (FBM), which leads to the reactive metabolite, 3-carbamoyl-2-phenylpropion-aldehyde. This aldehyde carbamate was suggested to be the reactive intermediate in the oxidation of 2-phenyl-1,3-propanediol monocarbamate to the major human metabolite 3-carbamoyl-2-phenylpropionic acid. In addition, the aldehyde carbamate was found to undergo spontaneous elimination to 2-phenylpropenal, commonly known as atropaldehyde. Moreover, atropaldehyde was proposed to play a role in the development of toxicity during FBM therapy. Evidence for atropaldehyde formation in vivo was reported with the identification of modified N-acetyl-cysteine conjugates of atropaldehyde in both human and rat urine after FBM administration. Identification of the atropaldehyde-derived mercapturic acids in urine after FBM administration is consistent with the hypothesis that atropaldehyde is formed in vivo and that it reacts with thiol nucleophiles. Based on the hypothesis that the potential for toxicity will correlate to the amount of atropaldehyde formed, we sought to develop an analytic method that would quantify the amount of relevant metabolites excreted in patient urine. METHODS: We summarize the results of an LC/MS method used to quantify FBM, 3-carbamoyl-2-phenylpropionic acid and two atropaldehyde-derived mercapturic acids in the patient population. RESULTS: Analysis was performed on 31 patients undergoing FBM therapy. The absolute quantities of FBM and three metabolites were measured. CONCLUSIONS: This method demonstrated sufficient precision for the identification of patients exhibiting "abnormal" levels of atropaldehyde conjugates and may hold potential for patient monitoring.     

Technical Exhibits

Some important but little-emphasized nutritional aspects of gastrointestinal physiology are discussed. Experimental studies which form the basis for present understanding of fluid and electrolyte problems are reviewed briefly. Other topics include harmful and beneficial effects of gastrointestinal bacteria, protein-losing enteropathies, and nutritional problems associated with gastrointestinal resection.     

Novel 16‐channel receive coil array for accelerated upper airway MRI at 3 Tesla

Upper airway MRI can provide a noninvasive assessment of speech and swallowing disorders and sleep apnea. Recent work has demonstrated the value of high‐resolution three‐dimensional imaging and dynamic two‐dimensional imaging and the importance of further improvements in spatio‐temporal resolution. The purpose of the study was to describe a novel 16‐channel 3 Tesla receive coil that is highly sensitive to the human upper airway and investigate the performance of accelerated upper airway MRI with the coil. In three‐dimensional imaging of the upper airway during static posture, 6‐fold acceleration is demonstrated using parallel imaging, potentially leading to capturing a whole three‐dimensional vocal tract with 1.25 mm isotropic resolution within 9 sec of sustained sound production. Midsagittal spiral parallel imaging of vocal tract dynamics during natural speech production is demonstrated with 2 × 2 mm² in‐plane spatial and 84 ms temporal resolution. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Robotic colorectal surgery: hype or new hope? A systematic review of robotics in colorectal surgery

Aim Robotic colorectal surgery is an emerging field and may offer a solution to some of the difficulties inherent to conventional laparoscopic surgery. The aim of this review is to provide a comprehensive and critical analysis of the available literature on the use of robotic technology in colorectal surgery. Method Studies reporting outcomes of robotic colorectal surgery were identified by systematic searches of electronic databases. Outcomes examined included operating time, length of stay, blood loss, complications, cost, oncological outcome, and conversion rates. Results Seventeen Studies (nine case series, seven comparative studies, one randomized controlled trial) describing 288 procedures were identified and reviewed. Study heterogeneity precluded a meta‐analysis of the data. Robotic procedures tend to take longer and cost more, but may reduce the length of stay, blood loss, and conversion rates. Complication profiles and short‐term oncological outcomes are similar to laparoscopic surgery. Conclusion Robotic colorectal surgery is a promising field and may provide a powerful additional tool for optimal management of more challenging pathology, including rectal cancer. Further studies are required to better define its role.     

Illness experience,depression, and anxiety in chronic fatigue syndrome

Objective: Given the high rate of psychiatric comorbidity with chronic fatigue syndrome (CFS), we considered two possible correlates of anxiety and depression: lack of illness legitimization and beliefs about limiting physical activity. Method: A total of 105 people diagnosed with CFS reported on their experiences with medical professionals and their beliefs about recovery and completed the depression and anxiety subscales of the Brief Symptom Inventory. Results: Those who said that their physician did not legitimize their illness (36%) had higher depression and anxiety scores (P's<.05) than their counterparts. Those who believed that limiting their physical exertion was the path to recovery (55%) had lower depression and anxiety scores (P's<.01) than their counterparts. Conclusion: Lack of illness legitimization ranked high as a source of dissatisfaction for CFS patients, and it may aggravate psychiatric morbidity. Many CFS patients believed that staying within what they felt to be their physical limits would improve their condition. This belief, and possibly an accompanying sense of control over their symptoms, may alleviate psychiatric morbidity.     

Inconsistency in evidentiary standards for medical testimony: disorder in the courts

Jerome P. Kassirer, MD; Joe S. Cecil, PhD,JD

JAMA. 2002;288:1382-1387.

Several recent decisions by the US Supreme Court have strengthened the ability of federal courts to consider medical testimony regarding injuries associated with exposure to toxic substances. Judges are expected to examine the basis of all expert testimony before it is introduced at trial to ensure that it meets the same standards of intellectual rigor that professionals use outside the courtroom. However, courts have been inconsistent in measuring this testimony against the standards of medical practice, especially when courts consider testimony that is not supported by clinical trials or epidemiological studies. A number of courts have required standards for expert testimony that exceed those that physicians use in ordinary clinical decision making. In this article, we illustrate such inconsistencies across federal courts by contrasting different decisions in cases involving similar facts and expert testimony. We argue that there may be good reason to require a standard of admissibility that exceeds the standards of ordinary clinical decision making, but such requirements are not faithful to the mandate of the Supreme Court. Courts with especially demanding standards are misled if they believe that they are fairly representing medical practice. Physicians should respond by correcting courts' misinterpretations of medical practice and assisting in the development of legal standards that encourage thoughtful and informed consideration of medical testimony by judges and juries.

     

Maternal serum creatine kinase does not predict tubal pregnancy

Purpose: Our purpose was to validate prospectively the predictive value of maternal serum creatine kinase in the evaluation of ectopic pregnancy. Methods: Fifty-one consecutive pregnant first-trimester patients who presented for suspected abnormal pregnancy were enrolled. Maternal serum samples were obtained and assayed for creatine kinase. Patients were subsequently evaluated for abnormal pregnancy by serial quantitative hCG levels, transvaginal ultrasonography, and surgery when appropriate. A receiver operating characteristic (ROC) curve was generated comparing intrauterine to extrauterine (ectopic) pregnancy. Results: Of 51 patients, 18 had an ectopic pregnancy, 16 had a spontaneous abortion, and 17 had an ongoing intrauterine pregnancy. The ROC curve revealed that maternal serum creatine kinase had no ability to predict ectopic pregnancy. Conclusions: Maternal serum creatine kinase is not a reliable predictor of tubal pregnancy.Presented at the Forty-Second Annual Meeting of the Society for Gynecological Investigation, March 15–18, 1995, Chicago, Illinois.