Polygenic inheritance of otosclerosis.

Polygenic inheritance of otosclerosis. A large family has been studied and its pedigree traced for six generations. Fifteen relatives are known  to have had otosclerosis. Of these, the only six individuals who developed this disease before the age of twenty were offspring of second-cousin marriages. Other children in the extended family developed the disease later and may have had somewhat less severe symptoms. The original hypothesis that the severe, early onset cases occurred among those homozygous for a monogenic trait became improbable on mathematical analysis. We conclude that the inheritance of otosclerosis in this family is polygenic and probably multifactorial. Individuals marrying within the family have a greatly increased risk of giving birth to children who will develop otosclerosis early, and perhaps severly. Those who marry outside the family have a greatly decreased risk. They do, of course have a higher risk than the general population of having children who will at some point experience a conductive hearing loss.


Adenocarcinoma originating in the thyroglossal duct. Eighty-six cases of carcinoma of the thyroglossal duct have been reported in the literature, most of these being well-differentiated adenocarcinomas. Three new cases of the latter type are presented. Cases where carcinoma of the thyroglossal duct is suspected should be investigated with fine-needle biopsy, thyroid scintigraphy, skeletal and pulmonary X-ray, determination of TSH, T 3, PBI and blood serum calcium. The treatment of well-differentiated adenocarcinomas is a combination of surgical and medical procedures.


Protein and cellular pattern of glue ear secretions. Analysis of glue ear secretions showed that the total protein content was slightly higher than in serum and that in the effusion proteins appeared that were specific to the mucosal secretion. The cellular analysis of samples from 137 ears showed that lymphocytes and neutrophils predominated, and that monocytes and phagocytes appeared in most specimens. Eosinophils and mast cells were rare. Staining of bacteria in the smear was seen in one-third of the slides and the mucus strands were numerous. The cellular picture is in line with an infective etiology.


Immunoglobulin E in chronic middle ear effusions. A total of 61 middle ear effusions and matched sera obtained from patients suffering from chronic otitis media with effusions (OME) was examined for IgE and other immunoglobulins to see if a reaginic antibody is involved in OME. The IgE levels were determined by the Phadebas IgE radioimmunoassay test. Excluding one patient who had extremely high IgE as a result of parasitosis, there were only three cases which showed marginally increased serum IgE levels. Elevated IgE levels in sera and/or in effusions were unrelated to a history of allergy. The mucoid effusions had significantly higher effusion levels than the levels in corresponding sera (p less than .0005). Fourteen percent of the cases examined showed effusion IgE levels five times or more higher than serum levels. Biopsy specimens of these patients showed numerous degranulating mast cells. Only two specimens showed eosinophilic infiltration. It is suggested that the IgE is produced locally by the mucosa in mucoid-type effusions and may have been involved in mast cell degranulation. However, this study cannot confirm the allergic nature of the OME.


Antimicrobial factors and bacterial correlation in chronic otitis media with effusion. Analyses of effusions and sera from patients with otitis media with effusion demonstrated local production in the middle ear of lysozyme, IgA and IgG. The effusion IgM was markedly elevated in some patients, also indicating local production. Complement C3 with rare exception was significantly lower in effusions than sera, suggesting utilization of complement in the middle ear, perhaps in conjunction with antibodies. The presence of high levels of lysozyme and immunoglobulins in effusions correlates with the low isolation rate of microorganisms in culture and may influence survival of organisms in the middle ear.


Classification of middle ear effusions.

Classification of middle ear effusions. Proper use of terminology and classification of various categories of effusion throughout the world is necessary if we are to obtain dissemination of pertinent scientific and clinical information and to make progress in understanding and eradicating this widespread group of diseases. The general term, middle ear effusion, and the categories serous, mucoid, and purulent are suggested to describe collections of fluid in the middle ear; the use of other descriptive terms should be influenced by the nature of the clinical, cytologic, bacteriologic, histopathologic and chemical findings in the fluid and lining membrane of the middle ear.


Microbiology in serous otitis media.

Microbiology in serous otitis media. It is now established that serous otitis media (SOM) is an inflammatory reaction of the mucosa of the middle ear. A number of microbiological factors are contributory causes. It is clear, among other things, that the microbiologic environment in the nasopharynx in SOM is the same as that in acute otitis media. Neither adenoidectomy and tonsillectomy nor treatiment with conventional chemotherapeutics has proved effective for eradicating pathogenic bacteria from the nasopharynx. Intense research to find new antibiotics and effective means may be one way of getting us out of our present therapeutic dilemma. Other possibilities are to try to produce polyvalent bacterial vaccines and to increase our knowledge of the immunology of the nasopharynx.


Physiology of the Eustachian tube.

Physiology of the Eustachian tube. A method for studying the middle ear mechanics is described. The method permits continuous recording of the volume deviation of the drum in relation to the neutral position, both on change in the ambient pressure and in the pressure in the middle ear. One hundred and two volunteers with normal hearing, i.e., a normal audiogram and normal ear findings, were tested repeatedly. This is the most detailed and extensive investigation hitherto performed on healthy volunteers with the aid of a sophisticated, reliable scientific method not suitable for clinical use.


Normal gas exchange in the human middle ear. Different kinds of biological gas pockets and the special character of the middle ear as a gas pocket are discussed. The pattern of gas absorption from the normal middle ear and from ears with blocked Eustachian tubes is presented. The amount of gas leaving the ear by diffusion and the resulting underpressure from this process are determined. The composition of air in the ear is compared to that in experimental gas pockets and the role of the partial pressures of CO2 and O2 in secretory otitis media is discussed.


Study of the ventilation of middle ear using radioactive xenon. The greatest contribution of nuclear medicine has been to make possible dynamic measurements of regional function. It is conceivable that if this technology could be successfully used to measure the ventilation and clearance of the middle ear, answers to some of the most crucial problems in otology may be found. The objectives of this paper are three-fold: 1) A descriptive account of radiotracers and radiodetectors with emphasis on Xenon133. 2) The development of scintillographic techniques for the dynamic study of the ventilation of the ear and sinuses. 3) The methods that are being explored for the quantification of these functions.


Eustachian tube ventilatory function in children. In order to establish a simple stimulus-response characteristic of Eustachian tube physiology in children, the tubal ventilatory function was studied. The parameters of active and passive opening of the tube were measured for three groups of patients with nonintact tympanic membranes. The group with traumatic perforations of the tympanic membrane without any history of middle ear disease had better active equilibration function than the group with chronic otitis media and perforations of the tympanic membrane and the group with tympanostomy tubes in the tympanic membrane. Quantitatively, this could be expressed in terms of residual positive pressures. In the study of repeated inflation of the middle ear, all groups had lower second opening pressures which are attributed to the effect of surface forces.


Middle ear ventilation in secretory otitis media. The Eustachian tube function was determined repeatedly in 42 patients during as well as after the course of secretory otitis media. Air pressure equalization technique and impedance audiometry were used. Also the size of the mastoid air cell system was determined. It was found that poor tubal function and a small mastoid air cell system are signficance findings in these ears.


Concepts on the pathogenesis of middle ear effusions. Several concepts related to the pathogenesis of middle ear effusions are postulated. The mechanisms proposed are based on an understanding of fluid mechanics. A flask with a long, narrow neck is presented as a model of the Eustachian tube-middle ear-mastoid system. Fluid flow into and out of the flask is dependent upon the pressure gradient, compliance of the narrow neck and whether or not the bulbous portion is intact. It is suggested that locking of the tube may be dependent upon the speed of the application of the negative pressure and the compliance. Eustachian tube opening appears to be related not only to active muscle forces but may also be dependent upon the presence of a pressure gradient which passively assists tubal function. It is proposed that middle ear effusions result from reflux, aspiration or insufflation of nasopharyngeal secretions (acute otitis media), or from persistent functional or mechanical Eustachian tube obstruction (secretory otitis media) or both.


Pediatrician's view of middle ear effusions: more questions than answers. Although middle ear effusion is the most common of the chronic conditions encountered in pediatric practice, it frequently goes unrecognized, and relatively little is known about its epidemiology or its natural history. More importantly, the impact of middle ear effusion on the overall well-being of infants and children, and on their cognitive and language development, remains essentially unexplored. In part because of these gaps in our knowledge, and also because prospective, controlled treatment trials have not been reported, uncertainty and controversy exist concerning: 1) the necessity, in many instances, of treating middle ear effusion; 2) the choice of various treatment methods; and 3) the timing of those treatments that are undertaken. Finally, the widespread use of adenoidectomy to prevent middle ear inflammation is seriously lacking in supporting evidence. A few reported studies bear on some of these questions, but both their scope and the information they provide are limited. In order to resolve important prognostic and treatment issues concerning middle ear effusion during infancy and childhood, carefully designed epidemiologic and clinical studies of types not hitherto reported are urgently needed.


Tympanometry: application and interpretation. The poor relationship between hearing loss and ear disease minimizes the effectiveness of audiometry as a technique for the identification of middle ear disorders. Tympanometry has been shown to be a highly sensitive technique for the identification of and differentiation between middle ear disorders. It is particularly useful in a pediatric population where ear disease is so frequently encountered. The interpretation of tympanometry on the basis of a descriptive analysis of tympanograms is proposed as opposed to a coded typing system. Descriptive analysis views the pathological effects of middle ear diseases on pressure peaks, amplitude and shape of tympanograms.


Autonomic stimulation, osmolarity and prostaglandin effects in the Eustachian tube. Stimulation of the vidian nerve in the dog induced an apparent vasodilation in the mucosa of the Eustachian tube. It is presumed that these parasympathetic fibers course from the greater petrosal nerve through the vidian to the sphenopalatine ganglion. The pharyngeal nerve arises from the ganglion and innervates the mucosa of the tube. Perfusion of the dog's Eustachian tube with solutions of various osmolarities caused a shrinking or swelling of the tube mucosa. Ten percent alterations in the concentration of saline, Ringer's or isotonic KCl produced a hypo- or hypertonic effect. Systemic administration of osmotic diuretics was shown to remove water from normal and edematous tubal mucosa. An agent in human middle ear effusions was found to contract smooth muscle. The behavior of this agent in pharmacological tests suggested the presence of prostaglandins (PG). The effusions were tested for the presence of other inflammatory mediators such as bradykinin, acetylcholine and histamine. These were felt to be absent or present in small amounts. A radioimmune assay of pooled samples of middle ear effusions revealed the presence of several PG, notably PGF2alpha and PGE2. There appeared to be a higher concentration of PG in mucoid effusions than serous effusions. The inflammatory capabilities of these agents are mentioned.


School screening for middle ear effusions. Early detection of middle ear effusions is highly desirable not only from a medical standpoint, but also educationally, psychologically and socially. Present methods do not appear to be adequate and the proposal has been made that impedance measurement may be of greater effectiveness in detecting abnormalities of middle ear function. Eighty children have been studied over a period of six to seven years during which time the middle ear function has been monitored by means of an impedance meter. Approximately one-half of the children have not indicated any variation in middle ear function over the period of observation. About one-third of the children have had isolated episodes of effusion from which they have recovered spontaneously and without adverse effects. The remaining one-sixth have had repeated episodes of effusion or persistent middle ear malfunction for substantial periods of time. Observation of the middle ear muscle reflexes at suitably chosen time intervals appears to have promise as a method of early detection of effusion in the middle ear.


Improved diagnosis of middle ear effusions employing the objective otoscope. A new quantitative diagnostic otoscope presently under development supplements the conventional otoscopic examination with a quantitative pneumatic system and objective measurements derived from tympanometry. The instrument provides information to assist in the diagnosis of the presence of middle ear effusion (MEE), the middle ear pressure and tympanic membrane status during the visual examination. Uncertainty introduced by subjective judgement involved with traditional pneumatic otoscopy is eliminated enabling a more rapid and accurate diagnosis. Clinical evaluations were performed in which 92% accuracy was achieved for the diagnosis of the presence of MEE in 38 ears. The results were verified at myringotomy. The instrument is being designed for use by physicians and paraprofessionals.


Cytologic and immunologic response revealed in middle ear effusions. The cellular patterns of middle ear effusions which reveal lymphocytic transformation and macrophage activity, help to explain the basic pathologic condition. This appears to be a typical delayed-type hypersensitivity reaction. The nasal cytogram often contributes to the understanding of the aural pathology. The treatment must be individualized with an effort to find the source of antigenic stimulation causing the response, and, in turns, support the systemic immune system of the patient in definitive ways, as have been suggested.


Tympanometry revealing middle ear pathology. In order to evaluate the usefulness of impedance audiometry as a screening method for school children, two different pilot studies were performed. The results indicated that impedance audiometry (tympanometry and stapedius reflex test) was more efficient than otoscopy and pure tone screening in the detection of ears with secretory otitis media (SOM). In order to gain some more experience, an extended study of 800 7-year-olds was performed. The results from this investigation showed 6.5% pathological values with pure tone screening, 13.5% pathological values with tympanometry and 32% elevated or nonelicitable stapedius reflexes. Analysis of our observations indicates that the stapedius reflex may be too sensitive a test to be used as a screening method. Tympanometry, however, is recommended as a complement to pure tone screening in screening of children. A 6-12 months follow-up was also performed on 357 ears in which an initial study had shown a middle ear pressure of less than or equal to -100 mm H2O. At the repeated test 20% had pathological pure tone screening, 40% had a middle ear pressure of less than or equal to -100 mm H2O, 57% had elevated or nonelicitable stapedius reflexes, and 14% had middle ear effusion. The high frequency of persisting abnormal middle ear pressure and effusion in these 357 ears suggests that a middle ear pressure of less than or equal to -100 mm H2O can be a predisposing factor for SOM. In an experimental study on human temporal bones it was demonstrated that the tympanogram preserves its original appearance when the water level is low in the middle ear, while a higher level gives rise to a pathological tympanogram. It is also demonstrated that there is a discrepancy between the tympanometrically, indirectly recorded middle ear pressure and the middle ear pressure as measured manometrically, directly from the middle ear.


Anatomy of the normal and cleft palate Eustachian tube. This report presents preliminary findings from a study of cleft palate and noncleft palate human fetuses to determine whether differences in Eustachian tube and cranial base structures could be found which might explain the universal appearance of otitis media in infants with cleft palate. Differences were found which are consistent with the previous hypothesis of reduced elasticity in the Eustachian tube. Principal findings included medial to lateral compression of the tube and reduced tubal width.


Myringostomy for middle ear effusions. Results of a two-year study. From 1972 to 1974, 736 children had tympanostomy tubes inserted for chronic serous otitis media resistant to medical therapy. The total number of ears involved was 2,237. The cleft palate patients constituted 8.8% of the total and had 15.4% of all procedures. Patients with allergy comprised 19% of the total population and had a higher incidence of otitis media following tube insertion. Adenoidectomy was performed in 44% of all patients and 35% of these required further tube insertions, suggesting that adenoidectomy in combination with tube insertion is not necessarily the primary treatment of choice. Children under six made up 78.5% of the total. The most common complication, a draining ear with an incidence of 15.1% was treated successfully with aqueous Merthiolate irrigations. There were 14 tympanic membrane perforations.


Comparative study of various ventilating tubes. In less than 20 years, insertion of middle ear ventilating tubes has become perhaps the most common operative procedure. It was not possible to find a study that adequately compares the performance of the many different types of tympanostomy tubes available. The ideal ventilating tube is defined; it has not yet been designed.


Antibacterial therapy and middle ear effusions. Antimicrobial drugs chosen for their activity against the causative pathogens of otitis media provide effective treatment for acute attacks. Prolonged administration of some of these agents has recently been shown to be of value in the prevention of symptomatic otitis. The role of drug therapy in the management of chronic or recurrent middle ear effusion is unknown at present.


Clinical results and complications of tympanostomy. Tympanostomy tube treatment was used in 181 patients on 323 ears and a followup study was made as an average three years and two months later. Sixty-five percent of the ears had healed completely and in these the average tube treatment time had been 11.3 months. In 22% the tubes were still in position, the average time for treatment being 24.2 months. Five percent showed purulent discharge and recurrence of the glue ear was noted in 3%. A dry perforation developed in five patients. Cholesteatoma was seen in four ears but in only one of these it may have been related to the location of the tube at the posterior drum margin.


Adenoidectomy in relation to otitis media. Past studies of the efficacy of adenoidectomy in the management of children with otitis media have been inconclusive due to significant limitations in experimental design. At the Children's Hospital of Pittsburgh, the effect of adenoidectomy on the outcome of otitis media is currently being studied in a prospective manner. An attempt is being made to document and to control those factors cited as lacking in the previous studies. This report describes the techniques for assessment of nasal and Eustachian tube function and for the completeness of adenoidectomy.


Membrane ventilating tube for the middle ear. A pilot study was conducted to evaluate the efficacy of a membrane ventilating tube as a Eustachian tube prosthesis in 20 patients with otitis media. The design was based partly on assumptions since many of the physiological parameters required to calculate the gas transport processes have not been previously reported. An elementary gas transport model with assumed partial pressures of gases was developed. A semipermeable membrane covering a tympanostomy tube was fashioned and used to ventilate the middle ear cavity. From this preliminary investigation, the device successfully maintained atmospheric pressures in the tympanum, compensated for Eustachian tube malfunction, prevented otorrhea and recurrence of middle ear effusions.


Management of middle ear effusions in infants with cleft palate. Middle ear effusion is now generally recognized as a virtually universal complication in infants with cleft palate. Such infants may therefore be assumed to experience conductive hearing loss of some degree or other throughout infancy. Hoping to prevent not only deficits in intellectual and language development, but also permanent otic and auditory handicaps, we have routinely treated such infants as early as practicable with myringotomy and tympanostomy tube insertion. Subsequently, we have repeated the operation whenever blockage or extrusion of the tubes resulted in recurrence of persistent effusion. In this manner we have been able to maintain most infants in satisfactory middle ear status most of the time. Otorrhea, however, has been a frequent complication. Preliminary findings suggest that infants managed according to this regimen may eventually develop better language function than those not receiving such management. A current study is designed to test the advantages and disadvantages that might result from deferring the initial routine myringotomy until somewhate later in infancy.


Mastoidectomy and epitympanotomy.

Mastoidectomy and epitympanotomy. The procedure of mastoidectomy and epitympanotomy effected a two-year arrest of serous otitis media and correction of a refractory retraction pocket in 12 out of 20 patients with one patient lost to follow-up. Each mastoid and epitympanum was extensively involved with chronically inflamed tissue which surrounded the ossicles and chorda tympani nerve.


Blue ear drum and its management.

Blue ear drum and its management. The "blue ear drum" generally refers to a condition in which blood or blood products are found in the middle ear. After all possible causes for hemotympanum, including blood dyscrasias and trauma are searched for and ruled out, the patient may have chronic serous otitis media accompanied by bloody effusion. Treatment for all of these patients is conservative, consisting of medical therapy and, if need be, myringotomy and insertion of ventilation tubes. In spite of proper treatment, rarely the condition may progress, over a long period of time, to a state of intractability. Characteristic findings are a hypocellular mastoid, hyperplastic and metaplastic mucoperiosteal lining, including the presence of glands and cysts and cholesterin granuloma. The recommended procedure is a modified radical mastoidectomy, placement of silicone rubber sheeting in the middle ear and insertion of a ventilation tube. It is to be emphasized that mastoid surgery is rarely indicated for these patients and only after all else has failed.


Ultrastructure of the middle ear mucosa. Histologic studies of recent years have definitely concluded that the epithelium of the middle ear is a modified respiratory epithelium with ciliated and secretory cells, including goblet cells. These cells, like the ciliated cells, are developd from the basal cell and are just ordinary secretory cells completely filled with secretory granules. For different reasons it is postulated, that the dark secretory granules are prestages of the actual secretory product presenting as light granules and that dark and light granules do not represent different secretory capacities of the cell. The subepithelial layer which consists of loose connective tissue is a structure of just as great importance as the epithelial layer.


Functional morphology of the mucosa of the middle ear and Eustachian tube. A review of available histological, histochemical and ultrastructural data on middle ear mucosa and the Eustachian tube was made to provide a broad cellular basis for understanding middle ear effusions. The presence of mucociliary defense system in a large part of the Eustachian tube and middle ear is seen as the first line of defense. Secretion by the mucosa has a profound biological significance. Immunoglobulins A, G, and even E and M are produced locally by the mucosa and may contribute to the immunodefense of the middle ear. Secretory lysozyme is also produced by the mucosa and may contribute enzymatic defense of the ear. Mucosal immunoglobulins and lysozyme are significantly elevated in the effusions, which would imply that local defense systems are hyperactive in OME. It also appears that these increases are related to the increase of the secretory cell population. It is also suspected that auditory surface-active agent is produced locally and may facilitate normal function of the tube. The middle ear also can transport macromolecules very rapidly across intact mucosal epithelium. The large numbers of tissue and wandering macrophages found in the mucosa and effusions would also imply that the middle ear is capable of efficient phagocytosis, which may be involved in processing antigen.


Goblet cell population in the normal middle ear and Eustachian tube of children and adults. On 54 temporal bones from entirely normal prematures and newborn infants, children, and adults, 30,000 to 90,000 counts of goblet cells were done in different parts of the Eustachian tube and middle ear. In the Eustachian tube, normal prematures showed a very low density of goblet cells in all localities, increasing in the pharyngeal parts gradually through childhood and reaching in the normal adult a very high density in the pharyngeal orifice. There are no differences in density between the medial and lateral wall, but in some parts a decrease of density towards the tubal roof. In the middle ear the density is low in normal prematures, increasing slightly in infants, and decreasing again during the age range 7-14 years and in adults. Goblet cells are present in all middle-ear localities, but in markedly decreasing density in this sequence: hypotympanum anteriorly, posteriorly, promontory anteriorly, in the middle, epitympanum, niche of oval window, antrum, niche of round window, mastoid process, incus, and promontory posteriorly.


Autonomic nervous system of the cat middle ear mucosa. The autonomic nerves of the cat middle ear mucosa were studied by the methods of surface preparation, histochemistry and electron microscopy. The tympanic nerve was found to contain large myelinated fibers probably of a sensory nature. Other sympathetic bundles consisted primarily of unmyelinated fibers with a sparse distribution of myelinated fibers. The inferior tympanic artery was accompanied by many vasomotor nerves and its branches were also innervated predominantly by adrenergic fibers. A dense neural network which showed acetylcholinesterase activity was found in the mucosa around the Eustachian tube orifice. These nerves consisted of several unmyelinated fibers encapsulated by a single Schwann cell just below the epithelium. The fine structure of the small ganglions of the tympanic plexus revealed that the cholinergic nerve endings synapse with the cell body of the ganglion. This finding suggests that these ganglions are autonomic.


Clearance of middle ear effusions and middle ear pressures. Twenty-six children presenting bilateral secretory otitis media (SOM) had ventilating tubes inserted into both middle ears. Mucus was, however, aspirated only from one ear, the right side. The vast majority of ears right and left were seen to have cleared their effusion equally well regardless of whether they were aspirated on not. This experiment points toward the essential intactness of the mucociliary system and the patency of the lumen of the Eustachian tube in SOM. Promotion of middle ear clearance through ventilation, which reminds one of the second opening in a beer can, does obviously suggest the relief of some negative pressure. Direct manometric measurements of SOM middle pressure were performed in 41 ears showing negative pressure averaging --1.7 mm H2O, this range being two orders of magnitude less than tympanometric measurements. Normal ears did not have even such a small negative pressure. The validity of these direct manometric measurements was checked against a model of the middle ear. Tympanometry, which is a valid diagnostic tool, does indicate in all probability the presence of middle ear effusion due to its rheologic effects on the drum and ossicles rather than the measure of actual middle ear pressures. This is determined by the fact that direct needling of the middle ear, or even the insertion of a ventilating tube, did not change tympanometric values but aspiration of part of the effusion did: indeed the latter tended to bring manometry to normal values.


Atelectasis and secretory otitis media.

Atelectasis and secretory otitis media. That condition where the tympanic membrane is displaced toward the promontory is termed atelectasis. Thirty-seven patients (61 ears) showing various degrees of atelectasis graded from stage 1 to stage 4 were studied. Atelectatic drums are an inflammatory phenomenon occurring in underventilated ears. This conclusion is reached by considering the reversibility of the atelectasis upon ventilation; while the inflammatory factor can be deduced from the history and histopathology of the atelectatic drum, as well as the histology of the necrosed incus, the latter occurs in over a third of our cases. Also pneumatization of the mastoid is almost never present. Twelve (21%) of the ears treated did indeed develop a perforation at one time or another (two had cholesteatomas). Chronic granulating external otitis with specific features occurred in 15% of cases. The characteristics of these ears and their case histories lead us to view atelectatic ears as part of the otitis media syndrome, where their place is somehow transitional between secretory otitis media on the one hand and chronic otitis media on the other.


Role of perilymph in the early stage of serous otitis. After injection of an electron-dense tracer into the cerebrospinal fluid (CSF) the particles can be seen within the lymphatic spaces of the middle ear mucosa after a few minutes. They find their way via the well known communication routes from CSF to the perilymphatic spaces of the inner ear. From there they enter through open fluid spaces into the fibrocytic network of the round window membrane which stands in open relationship to the extracellular fluid spaces of the middle ear mucosa. They were drained to the regional lymph nodes by lymphatic vessels. When inducing a serous otitis by experimental obstruction of the Eustachian tube it could be demonstrated that the fluid within the middle ear cavity is partly coming from the CSF and perilymph. Later the healing process of the middle ear epithelium was studied after the onset of serous otitis with and without artificial ventilation of the middle ear.


Middle ear effusions: definitions and terminology. There are many confusing terms which presently apply to the group of clinical problems accompanied by middle ear effusion manifestations. Out of this chaos there is a need for logic and simplicity. All of the middle ear effusions are examples of the broadly descriptive categorical term "otitis media" meaning "inflammation" of the middle ear which includes examples of frank "infection" as well. Based upon clinical and laboratory observations there are essentially four types of intrinsically occurring middle ear fluid which, along with clinical findings, provide the means of identifying the clinically descriptive term which should be used: 1) serous fluid (serous otitis media); 2) mucoid fluid (mucoid otitis media, secretory otitis media, glue ear); 3) bloody fluid (barotrauma, aerotitis); 4) purulent fluid (purulent or suppurative otitis media); and 5) any combination of the above four (e.g., seropurulent otitis media, serosanguineous otitis media, mucopurulent otitis media, etc.).


Mortality and morbidity following road accidents. The results of a prospective study of the victims of road traffic accidents from the time of injury until their discharge from hospital or death are reported. Data on 2392 surviving hospital admissions and 344 deaths were collected over a period of one year from 12 hospitals covering a wide area in northern England.


The incidence and clinical significance of rectal polyps. Adenomata of the large bowel were discovered at proctosigmoidoscopy in 28 out of 1000 patients examined; this is a much lower frequency than those reported from American sources. The distribution and histological features of these tumours are considered and lack of correlation between the microscopic and macroscopic characters noted.


Middle ear effusion in experimental hypersensitivity. Monkeys which were transfused with human serum containing a specific antibody developed a clear, middle ear effusion when the appropriate antigen (ragweed) was insufflated into their middle ear space via the Eustachian tube. The typical histological changes expected to occur in an immediate type 1 immune response were present. Intracellular edema, capillary dilation, and an initial exudative reaction were all seen. Serum IgE levels were found to be significantly raised in the animal following passive sensitization. IgE was also present in the effusion, and IgE specific fluorescent mast and plasma cells were noted in the middle ear mucosa of the sensitized animals.


Secretory IgA and antibody activities in middle ear effusions. Secretory IgA (SIgA) was isolated from pooled middle ear effusions (MEE) and its antigenicity and subunit structure were found to be identical to those of SIgA in saliva, nasal secretion and colostrum. The calculated percentage of SIgA in the total IgA of effusions was approximately 11%. Although the SIgA antibodies against streptolysin and staphylolysin were very low when compared to that of IgG class in effusion, this finding confirmed that MEE is at least partially a result of local immunologic reactions. The IgE concentration did not become elevated in both the MEE and serum obtained from patients with otitis media with effusion. Specific reaginic activity against mites was found in 5 of 56 (8.9%) MEE. Our findings would not suggest the significant role of atopic allergy in the formation of MEE.


Diagnostic aspects in 117 patients treated surgically for thyroid carcinoma. A series of 117 patients operated on for thyroid carcinoma from 1969-1973 is compared with a previous series of 115 cases treated from 1956-1968, with the object of clarifying diagnostic aspects and indications for primary operation. In the group with papillary carcinomas there was a high peak of incidence among young patients both females and males aged 20 to 30 years. In the present series the incidence of metastases was less than in the previous series. Lymph node metastases in the neck were the only metastases in papillary and medullary carcinomas. The time interval between beginning of treatment and appearance of main symptoms had decreased noticeably. The pre- and peroperative diagnostic procedures employed made it possible to operate as the primary procedure in 78% of papillary, 100% medullary and 86% anaplastic tumours, but only in 52% of follicular carcinomas. The most common reason for diagnostic failure was that frozen section had not been performed during the primary operation. The value of both aspiration biopsy and frozen section was dependent on the histological type of the tumour; it was more reliable in papillary and anaplastic than in follicular carcinomas. The operability rate had not changed essentially, 94% of papillary and 85% of follicular, but only 24% of anaplastic primary tumours could be radically removed. The value of establishing a firm diagnosis is to be able to operate as a primary procedure in these tumours when less operative complications occur.


Peritoneal lavage with doxycycline in acute diffuse peritonitis. Peritoneal lavage with ten hourly repeated instillation-drainages of one litre lavage fluid containing 50 mg doxycycline (Vibramycin Pfizer) was carried out on six patients suffering from diffuse peritonitis due to perforated appendicitis. Bacteriological specimens were obtained both from the perforation in the appendix and the peritoneal fluid at operation and the doxycycline concentrations in blood and lavage fluid were determined at intervals up to 72 hours postoperatively. All the patients recovered, but the lavage was considered a failure in one case as a small abscess and multiple adhesions were found at reoperation 1 1/2 months later. Bacteriological swabs from the perforated appendix and the peritoneal fluid usually contained the same bacteriological species, and as a rule several species were isolated. Doxycycline compared favourably with ampicillin as regards bacterial sensitivity, but the difference was too slight to be of practical importance. Doxycycline was absorbed very rapidly from the peritoneal cavitiy, and due to its slow excretion a cumulation occurred. In this small series doxycycline did not appear to give any real advantage over ampicillin, but it may be considered the drug of choice in patients with penicillin allergy, and in those who fail to respond to ampicillin.


Results of regional portal infusion of 5-fluorouracil in patients with primary and secondary liver cancer. The survival of 47 patients with liver malignancies treated with continuous portal infusion of fluorouracil (5-FU) has been studied. 18 of them had been treated initially by hepatic artery ligation. Total mean survival was 9.4 months. Patients treated with hepatic artery ligation + 5-FU lived longer (mean 10.8 months) than those treated with 5-FU alone (7.4 months). The survival was longer than could be expected for patients treated for primary liver cancer or for liver metastases from colo-rectal cancer, when compared with the "untreated" group. It is concluded that continuous portal infusion of 5-FU appears to prolong survival in some groups of patients with malignant liver tumours. However, the influence of "unspecific, general" therapy is difficult to evaluate.


Retroperitoneal injuries of the duodenum caused by blunt abdominal trauma. Five patients with blunt retroperitoneal injury of the duodenum are presented. In three of them the trauma was caused by a traffic accident, the most common mechanism of such injuries. One patient died. The high index of suspicion is still the best indication for laparotomy in retroperitoneal injuries of the duodenum, because no typical finding or reliably diagnostic test could be demonstrated even in the present study. The proper treatment in less severe injuries of the retroperitoneal duodenum is evacuation of the hematoma or simple suture of the rupture with drainage and naso-gastric suction. Internal drainage as an afferent jejunostomy is sometimes necessary in the treatment of more severe injuries. Pancreatoduodenectomy is to be reserved for only the very severe duodenal injuries, where the head of the pancreas is badly crushed.


Intestinal blind pouch- and blind loop-syndrome in children operated previously for congenital duodenal obstruction. A follow-up study of 27 children operated for congenital duodenal obstruction (CDO) in years 1953-71 is presented. Nine children belonged to the intrinsic and 18 children to the extrinsic group of CDO. A total of 7 retrocolic, isoperistaltic, side-to-side duodeno-jejunostomy, 7 Ladd's operation, 8 duodenolysis, 2 reduction of midgut volvulus, 2 duodenostomy a.m. Morton and one gastro-jejunostomy were performed at the age of 1 day-15 years. The clinical and radiological examinations were performed 3-21 years (mean 10 years 2 months) after these operations. In 3 cases there was a moderate duodenal dilation, but reoperation was not necessary. During the follow-up period, one boy, now aged 8 years, developed a blind pouch-syndrome in the I portion of the duodenum containing a 5 X 5 cm phytobezoar 4 1/2 years after duodeno-jejunostomy. The frequency of blind pouch-syndrome after duodeno-jejunostomy was thus 1:7 or 14%. One girl, now aged 9 years, developed a blind loop-syndrome in the ileocaecal segment 3 months after side-to-side ileotransversostomy, which was performed from adhesion-obstruction after duodenolysis for malrotation I and CDO. Both the blind pouch- and the blind loop-deformation were resected and the children recovered well. To avoid blind pouch- and blind loop-deformations in the intestines, the anastomosis must be made wide enough, and especially in the surgery of the jejuno-ileo-colic region an end-to-end anastomosis is preferable.


A benign hepatocellular adenoma treated by extended right lobectomy. A 19-YEAR-OLD WOMAN WITH A LARGE BENIGN HEPATOCELLULAR ADENOMA IS PRESENTED. The initial symptom was continuous anaemia demanding transfusions twice a month. Coeliac angiography revealed the hepatic tumour, which was thought to be malignant. Angiography produced permanent paraplegia as a complication. The tumour was radically removed by an extended right lobectomy. The weight of the operation specimen was 2200 g. Histologically the differential diagnosis layed between benign hepatocellular adenoma and hepatocellular carcinoma. Postoperative stricture of the common duct developed as a complication of T-tube and was successfully treated at reoperation. Liver function became totally restored after the operation and after 5 years' follow-up there has been no tumour recurrence. The very rare benign hepatocellular adenomas are discussed.


Short-stay varicose vein surgery.

Short-stay varicose vein surgery. From 1967 patients attending for varicose vein surgery at the Meilahti Hospital Helsinki University Central Hospital, have been operated on on the day of admission, spend the following night in the bed ward and are discharged the morning after the operation. The operation is performed under general anaesthesia with as radical approach as possible stripping the long saphenous vein and, if required, the short saphenous vein, excising the superficial side branches and ligating incompetent perforators. In the study a follow-up examination was carried out on 2334 patients. Wound infections occurred in 1.8%. Two patients had transient arrhytmia, and one a late haemorrhage. More serious complications were absent. During the follow-up period 5.2% of patients were operated on for recurrent varicose veins. 84.6% were subjectively satisfied. The number of hospital days per patient averaged 1.2. It was possible to follow the above planned course of action in 93.4%. The organization and surgical technique can be recommended in order to achieve savings in hospital days and to produce permanent and good surgical results.


A comparison of dicloxacillin and ampicillin in the antibiotic prophylaxis of total hip replacement. The effect of two semi-synthetic penicillins, dicloxacillin and ampicillin was compared in systemic antibiotic prophylaxis in total hip replacement patients. The drugs were given in routine oral dosage for eight days to two patient groups each consisting of 50 patients. There was no fatality. In the ampicillin group there were three staphylococcal infections but no infections in the dicloxacillin group. Two of the infections occurred in reapplication cases leading to the loosening of the prosthesis. One infection appeared after a primary operation with a superficial recurrence 10 months later. In the ampicillin group, side effects were diagnosed in 12 cases and in the dicloxacillin group in one case.


Plasma calcium levels in pregnant Asian women. Plasma calcium, phosphorus, alkaline phosphatase, total protein, and albumin were measured during pregnancy in a group of Asian women living in the south of England and in a control group. The Asian women had slightly lower mean plasma calcium concentrations than the control group. Exposure of Asian women to sunshine appeared to be low, and it was inferred that they probably had little endogenous synthesis of cholecalciferol as a result. Both Asian and control subjects ingested similarly low amounts of vitamin D. The Asian women consumed greater amounts of phytate and vegetable fibres than the controls, and it is suggested that these substances may reduce absorption of insoluble lipids (including cholecalciferol) and calcium in a setting where the dietary intake and endogenous synthesis of vitamin D are already borderline for the subject's requirements.


A potential screening test for elevated serum amylase levels: preliminary communication. The use of an amylase-sensitive paper in a screening test for elevated serum amylase levels is described. The paper requires some modification before it can be used as a quantitative amylase assay, but even in its present form it will reliably identify samples with raised amylase levels. In tests with sera received routinely for amylase assay the paper characterised 80% of samples as Normal. Quantitative amylase assay confirmed the results, and thus, even with the present paper, if only the Medium or High sera were sent to the laboratory for full biochemical analysis there would be an 80% decrease in requests.


Preparation of 125I-thyroxine and 125I-triiodothyronine of high specific activity for the radioimmunoassay of serum total T4 and T3. A simple and inexpensive procedure for the preparation of high specific activity 125I radioiodinated triiodothyronine and thyroxine is described. The specific activities achieved are approximately 350 Ci/g for 125I-T4, and either 200 Ci/g for 125I-T3 depending on the reagents employed. The high specific activity 125I-T4 and 125I-T3 are suitable for the routine radioimmunoassay of serum total T3 and T4. When properly stored they have a self life of at least seven weeks.


Trimethoprim-sulfamethoxazole in murine toxoplasmosis. The combination trimethoprim-sulfamethoxazole had no greater activity in a murine model of toxoplasmosis than did sulfamethoxazole alone.


Antiviral activity of 10-carboxymethyl-9-acridanone. Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture.


Antimicrobial susceptibilities of shigellae isolated in Houston, Texas, in 1974. One hundred seventy-three strains of shigellae (113 Shigella sonnei, 56 S. flexneri, and four others) isolated in Houston during 1974 were tested for susceptibility to commonly used and newer antimicrobial agents. Forty-five percent of S. sonnei strains were susceptible to ampicillin, whereas 93% of S. flexneri strains were susceptible to that agent. S. sonnei and S. flexneri strains were equally susceptible to tetracycline (35 and 33%, respectively). All 173 strains were uniformly susceptible to quinoline drugs (cinoxacin, oxolinic acid, and nalidixic acid) and to trimethoprim-sulfamethoxazole. This study supports recent suggestions that the initial therapy of bacillary dysentery no longer should be ampicillin or tetracycline. It remains for field testing to determine whether quinoline agents or trimethoprim-sulfamethoxazole will be the treatment of choice.


Novel mechanism of resistance to folate analogues: ribonucleoside diphosphate reductase deficiency in bacteriophage T4. Some spontaneously occurring bacteriophage T4 mutants (far mutants) were able to form plaques in the presence of concentrations of folate analogues that completely inhibit plaque formation by wild-type phage T4. Some of these far mutants were shown to be ribonucleoside diphosphate (RDP) reductase (EC 1.17.4.1) deficient, and some independently isolated RDP reductase-deficient mutants (nrd mutants) were shown to be folate analogue resistant. The map positions of the RDP reductase-deficient far mutants were shown to be within the genes controlling the phage-induced RDP reductase activity.


Effect of cerulenin on growth and lipid metabolism of mycoplasmas. Cerulenin markedly inhibited the growth of Acholeplasma laidlawii. A. axanthum and A. granularum were less susceptible, whereas the sterol-requiring Mycoplasma species examined showed very little susceptibility. The inhibition was not reversed by the addition of long-chain fatty acids to the medium. At a concentration of 20 mug/ml, cerulenin inhibited the incorporation of [(14)C]acetate into A. laidlawii membrane lipids, but it had no effect on either protein or nucleic acid biosynthesis. Cerulenin inhibited both the de novo synthesis of long-chain fatty acids and the elongation of medium-chain fatty acids. As a result, carotenoid biosynthesis was stimulated, and increased amounts of oleic and elaidic acids were incorporated into membrane polar lipids. Our studies support the concept that cerulenin can serve as a useful tool for obtaining better control of fatty acid composition of A. laidlawii membranes.


Phosphonoacetic acid in the treatment of experimental ocular herpes simplex infections. Phosphonoacetic acid had a significant antiviral effect when applied topically, both in liquid and ointment preparations, on superficial herpetic keratitis in rabbits and was equally as effective as idoxuridine. It was also effective in the treatment of idoxuridine-resistant herpetic keratitis. Phosphonoacetic acid was not effective in the treatment of experimental herpetic iritis when applied topically but was significantly effective when administered intravenously and subconjunctivally. No significant local or systemic toxicity was encountered.


Hyperbaric oxygen exposures for intrahepatic abscesses produced in mice by nonsporeforming anaerobic bacteria. Hyperbaric oxygen exposures were evaluated for treatment of progressive liver abscesses produced by intraperitoneal injection of combined cultures of Fusobacterium necrophorum plus either Bacteroides fragilis subsp. fragilis or Fusobacterium nucleatum in a mouse model. Infected control and hyperbaric oxygen-exposed mice were autopsied 5 or 6 weeks after inoculation of bacteria and were assigned numerical pathology scores according to the number and size of abscesses present. Seventeen daily 3-h exposures to 100% O(2) at 2 atmospheres absolute pressure begun either 1 day or 1 week after injection of bacteria significantly reduced the number and size of abscesses among mice infected with either mixture of anaerobic organisms. Abscesses due to mixed fusobacteria were often completely resolved. These data support the efficacy of hyperbaric oxygen for treatment of mixed anaerobic infection produced by Bacteroides and Fusobacterium species and suggest its further evaluation as a potential alternate or adjunct to present therapy for certain types of serious anaerobic infection.


Relative morphological effects induced by cefoxitin and other beta-lactam antibiotics in vitro. Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams.


Rosamicin: in vitro activity against anaerobes and comparison with erythromycin. The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of Peptostreptococcus and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of Peptococcus, Clostridium, and gram-negative anaerobes. All strains of Bacteroides fragilis tested were inhibited by 4 mug of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against Fusobacterium nucleatum. Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted.


Unreliability of direct antibiotic susceptibility testing on wound exudates. Direct susceptibility testing was performed on 110 specimens of wound exudates. Growth was inadequate in 76 of these specimens. Of the remaining 34 specimens, only 5 produced results corresponding to those obtained by testing individual bacterial isolates by the Kirby-Bauer technique. This study confirms that direct susceptibility testing of wound exudates may provide misleading and clinically unreliable information on more than 95% of specimens.


Peritoneal transfer of thiamphenicol during peritoneal dialysis. The pharmacokinetics of thiamphenicol (TAP) was studied in 17 functionally anephric patients during peritoneal dialysis. Eleven patients were given single intramuscular injections of TAP in doses of 10 to 20 mg/kg of body weight. After this, serial blood samples and outflow dialysate collections were assayed for TAP by gas chromatography. The mean overall elimination rate constant was 0.036 +/- 0.007/h, the serum half time was 8.4 h, and the apparent volume of distribution was 71.0% (+/-14.39%) of the body weight. These parameters were not significantly different from those determined in anephric patients not on dialysis. The mean recovery of the administered TAP doses in the pooled outflow dialysate was 7.7% (+/-2.76%) over 22 h. In six other patients TAP was added to the inflow dialysate in concentrations of 10 to 20 mg/liter for 22 h. Throughout the dialysis periods, serum TAP levels did not rise above 4 mug/ml in transfer of TAP.


Pipemidic acid: its activities against various experimental infections. Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either widely disseminated or relatively localized infections with Staphylococcus aureus and a variety of gram-negative bacilli. The activity of pipemidic acid was always greater than that of piromidic and nalidixic acids; in infections with Pseudomonas aeruginosa and in bacilli resistant to the latter two drugs, pipemidic acid exhibited significant activity. In limited comparative studies, the activities of pipemidic acid were generally superior to the activities of cephalexin, ampicillin, and carbenicillin. Gentamicin, administered subcutaneously, was more active than pipemidic acid, given either orally or subcutaneously, against both systemic and localized infections with P. aeruginosa. The therapeutic accomplishments of pipemidic acid were attained with well-tolerated doses.


Effect of cephalothin on renal cortical concentrations of gentamicin in rats. Renal cortical concentrations of gentamicin were significantly lower in rats given this aminoglycoside and cephalothin simultaneously than in animals given gentamicin alone. This effect may be responsible, in part, for the reduction in nephrotoxicity reported previously in animals given the combination of drugs.


Minocycline resistance in Staphylococcus aureus: effect on phage susceptibility. Tetracycline-resistant strains of Staphylococcus aureus are minocycline sensitive, with the exception of strains susceptible to phages of the 83A/84/85 complex and some methicillin-resistant strains of other phage types. Strains of the 83A/84/85 complex yield mutants with increased minocycline resistance. Transduction of minocycline resistance into the susceptible strain RN 450 was obtained with donor strains possessing either markers for both extrachromosomal tetracycline resistance (tet) and chromosomal tetracycline + minocycline resistance (tmn R), or only for chromosomal tmn R resistance. The chromosomal marker was differentiated from the extrachromosomal marker by the lack of detectable extrachromosomal deoxyribonucleic acid after transfer into strain RN 450, transfer into a rec(+) strain, lack of transfer into rec(-) acceptor strain, and cotransduction with chromosomal determinants for guanine biosynthesis. Both chromosomal and extrachromosomal tetracycline resistance can be induced by tetracycline. Induction by tetracycline of chromosomal tetracycline resistance resulted in simultaneous induction of minocycline resistance. The mutation toward increased minocycline resistance (tmn --> tmn R) is a regulatory mutation toward constitutivity or semiconstitutivity. Constitutive resistance is dominant in tmn R/tet diploids. Transfer of the tet marker does not affect the phage susceptibility of the acceptor strain. The tmn R marker, originating from donor strains of the 83A/84/85 complex, renders strain RN 450 resistant to several typing phages, with the exception of phages of the 83A/84/85 complex. This could possibly account for the phage typing patterns of minocycline-resistant staphylococci.


Significant reduction in the incidence of phlebitis with buffered versus unbuffered cephalothin. Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone.


In vitro susceptibility comparisons and recommendations for oxolinic acid. Minimal inhibitory concentration and disk diffusion susceptibility studies were carried out with oxolinic acid to determine a recommended disk content for disk susceptibility testing. Regression curve analyses were performed with disks containing 1, 2, and 5 mug of oxolinic acid. Data suggest that the 5-mug disk more satisfactorily fulfills requirements for susceptibility testing than the 1- or 2-mug disks evaluated. Ultraviolet spectral analysis studies for absorption maxima and extinction coefficients were done to verify the authenticity and concentration of oxolinic acid in the aqueous solutions studied.


Effect of diethylpyrocarbonate on the antiviral and interferon-inducing activities of viral and nonviral agents. Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embryo cells were markedly reduced by the treatment. Target-organ treatment of Swiss Webster mice with DEPC-treated poly(I.C) produced higher levels of serum IF than did the same procedure with untreated poly(I.C), but the animals were not protected against vaccinial encephalitis. In contrast, DEPC-treated statolon protected the animals, although the peak serum IF level was significantly lower than in those treated with intact statolon. Nevertheless, the antiviral activity of statolon was also found to be mediated by IF, since no activity was seen in Vero cells. DEPC-treated single-stranded ribonucleic acid viruses failed to stimulate IF production, indicating that some viral factor(s) susceptible to DEPC is required for the stimulation observed with untreated viruses.


Antibacterial activity of cefuroxime, a new cephalosporin antibiotic, compared with that of cephaloridine, cephalothin, and cefamandole. The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against Staphylococcus aureus, Haemophilus influenzae, and most members of the Enterobacteriaceae. It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations.


Synergy of mecillinam (FL1060) with penicillins and cephalosporins against Proteus and Klebsiella, with observations on combinations with other antibiotics and against other bacterial species. Thirty-five strains each of Klebsiella and Proteus were tested for susceptibility to mecillinam alone and in combination with ampicillin, carbenicillin, cephalothin, and cefazolin. Antibiotics were considered to be synergistic when there was a >/=fourfold reduction in minimum inhibiting concentration of both antibiotics in the combination as compared with that of each antibiotic alone. Synergy of mecillinam with ampicillin, carbenicillin, cephalothin, and cefazolin was demonstrated against 2, 3, 7, and 8 of the 35 strains of Klebsiella and against 14, 14, 19, and 24 of the 35 strains of Proteus, respectively. Synergy against the isolates of Proteus was related to species, whereas against Klebsiella it was related to susceptibility of the isolates to mecillinam. Tests of combinations of mecillinam with other antibiotics on the same and different species indicated that synergy was related to the antibiotic, the species, and the strains of organisms tested.


Comparison of phlebitis produced by cephapirin and cephalothin. In a single-blinded study involving 120 patients neither the incidence nor severity of phlebitis observed with cephapirin and cephalothin was significantly different.


Comparative studies on the microbiological vitamin B12 assay at two laboratories. The turbidimetric methods in routine use at two laboratories for the microbiological assay of vitamin B12 have been compared. Attempts were made to standardize some major parts of the method, i.e., assay design, test strain (Lactobacillus leichmannii), test medium, and reference standard. The laboratories used different approaches to achieve efficient assay procedures. During a 6-year period four comparative experiments were carried out. In these experiments the vitamin B12 content of five different products was determined in a series of independent assays at each laboratory. A satisfactory degree of agreement (difference less than 5%) was found for four of these products.


Distribution of Bdellovibrio bacteriovorus in sewage works, river water, and sediments. Bdellovibrio was found in all liquid phases of the sewage works examined. The predator was also found in all the river sediments and sewage-polluted river waters examined but could not be found in some unpolluted river waters. Bdellovibrio was able to multiply on the high numbers of bacteria present in the aerobic percolating filter film but could not survive in anaerobic sludge. Similarly, the predator was present in the aerobic surface layers of river sediments but not in the anaerobic bottom layers. The major source of Bdellovibrio in the polluted rivers examined were sewage works effluents, and numbers in both river water and sediment were correlated with river water quality. It was unlikely that Bdellovibrio was important in reducing numbers of other bacteria in either sewage or river sediment.


Intestinal microflora in rats: isolation and characterization of strictly anaerobic bacteria requiring long-chain fatty acids. Three strains of strictly anaerobic bacteria, isolated from the cecal contents of rats, have strict requirements for long-chain fatty acids. The effect of exogenous fatty acids on the growth and fatty acid composition of the bacteria was examined. Biohydrogenation of linoleic acid into octadecenoic acid was observed. These observations suggest that long-chain fatty acids in the intestine are factors in controlling the localization and the population levels of indigenous bacteria in vivo in rats.


Blockage by acetylene of nitrous oxide reduction in Pseudomonas perfectomarinus. Suspensions of denitrifying cells of Pseudomonas perfectomarinus reduced nitrate and nitrate as expected to dinitrogen; but, in the presence of acetylene, nitrous oxide accumulated when nitrate or nitrate was reduced. When supplied at the outset in place of nitrate and nitrate, nitrous oxide was rapidly reduced to dinitrogen by cells incubated in anaerobic vessels in the absence of acetylene. In the presence of 0.01 atmospheres of acetylene, however, nitrous oxide was not reduced. Ethylene was not produced, nor did it influence the rate of nitrous oxide reduction when provided instead of acetylene. Cells exposed to 0.01 atmospheres of acetylene for as long as 400 min were able to reduce nitrous oxide after removal of acetylene at a rate comparable to that of cells not exposed to acetylene. Acetylene did not affect the production or functioning of assimilatory nitrate or nitrite reductase in axenic cultures of Enterobacter aerogenes or Trichoderma uride. While exposed to acetylene, bacteria in marine sediment slurries produced measurable quantities of nitrous oxide from glucose- or acetate-dependent reduction of added nitrate. Possible use of acetylene blockage for measurement of denitrification in unamended marine sediments is discussed.


Oil degradation in soil.

Oil degradation in soil. The environmental effects of adding certain selected petroleum products to field soils at widely separated geographical locations under optimum conditions for biodegradation were studied. The locations selected for study of soil biodegradation of six oils (used crankcase oil from cars, used crankcase oil from trucks, an Arabian Heavy crude oil, a Coastal Mix crude oil, a home heating oil no. 2, and a residual fuel oil no. 6) were Marcus Hook, Pennsylvania, Tulsa, Oklahoma, and Corpus Christi, Texas. The investigative process, covering a period of 1 year at each location, was conducted in 14 fields plots (1.7 by 3.0 m) to which the oils were added in a single application at a rate of 11.9 m3/4 X 10(3) m2. One-half of the plots at each location were fertilized, and the incorporation of the oils and fertilizers was accomplished with rototillers to a depth of 10 to 15 cm. Concentrations of all oils decreased significantly at all locations. The average reduction ranged from 48.5 to 90.0% depending upon the type of oil and location. Rates of degradation did not exceed 2.4 m3/4 X 10(3) m2 per month. Compositional changes in the oil with time were investigated using silica gel fractionation, gas chromatography, and ultraviolet absorbance. With the possible exception of the two fuel oils, the compositional changes were generally in the same direction for all of the oils. The silica gel fractionation and gravimetric data on residual oils show that all classes of compounds were degraded, but the more polar type degrade more slowly. Analysis of runoff water, leachate, and soils indicated that at the concentration applied no oil less was observed from these plots via water movement. No significant movement of lead compounds added to the soils in the used crankcase oils was observed. Significant increases in hydrocarbon-utilizing microorganisms were demonstrated in all treated plots using either the pure hydrocarbon, n-hexadecane, or the applied oils as the growth substrate. These increases were usually sustained throughout the year. Significant increases in hydrocarbon-utilizing fungi were not demonstrated by the plating technique used. The concentrations of residual oils or their oxidation products were of sufficient magnitude in the treated plots, 9 months after application, to cause significant inhibition of plant growth. From the data obtained, it was not possible to determine the type of compounds causing this inhibition or their long-term environmental effects.


Colonization of soil by Arthrobacter and Pseudomonas under varying conditions of water and nutrient availability as studied by plate counts and transmission electron microscopy. Arthrobacter globiformis and a Pseudomonas soil isolate were incubated separately and in combination in soil that had been presterilized by autoclaving. Growth and other responses of the cells in situ in this soil were monitored by plate counts and transmission electron microscopy examinations of cell sections. During the soil incubations, some of the samples were first allowed to dry and then were remoistened with water or with a dilute or a concentrated nutrient solution. Based on plate counts and ultrastructural analysis. Arthrobacter seemed to be in a non-multiplying coccoid-rod resting state and to be virtually immune to soil drying. Addition of a dilute nutrient solution helped maintain cell ultrastructure and prevent a low level of lysing that occurred in the absence of nutrient addition. Addition of a concentrated nutrient solution brought on cell multiplication as both coccoid-rods and long rods, but the ultimate form with further incubation was the coccoid-rod. The Pseudomonas strain suffered death and ultrastructural deterioration as water became less available. It responded by cell multiplication to an equal extent when either water or dilute nutrients were added, but possibly was able to give a growth response to nutritive amendment when a concentrated nutrient addition was made. The Arthrobacter was not affected by the presence of Pseudomonas in dual culture. The Pseudomonas, however, possibly suffered a nutritive deficiency under these conditions.


Natural protoplast Dunaliella as a source of protein. The protein content of once-washed pellets of Dunaliella primalecta was 35 to 48%. Protein quality was good. Electron microscopy confirmed the absence of a cell wall.


Microapplicator and micropipette for inoculation of the embryonated chicken egg. Aflatoxin G2 was used to test the speed and accuracy of the microapplicator and the micropipette. The 50% lethal dose of both assay systems was approximately the same, and 4.0 mug of G2 had an 85% lethal effect in both systems. The 50% lethal dose of the microapplicator and the micropipette was lower than that of the syringe but, of these, only the micropipette can combine the accuracy of the microapplicator and the speed of the syringe.


Epidermal activity in annular dermatophytosis. In five patients with annular tinea corporis, the tritated thymidine labeling indexes were determined in the rim, center, and intermediate areas of the lesion and compared with normal skin. Labeling indexes at the rim were much higher than those of normal skin (mean, 4.2 times). Labeling indexes elsewhere in the lesion were not significantly different from those of normal skin. Histologic examination showed epidermal thickening in all areas of the lesion as compared with normal skin. This study suggests that there is an increased epidermal turnover at the rim of annular dermatophytosis that may be important in the pathophysiology and morphogenesis of such lesions.


Cornifying Darier disease--a unique variant. I. Report of a case. A unique variant of Darier disease is described in which a patient was disabled by large, painful, cutaneous horns present on all extremities. The cornified lesions were distinguished by the presence of numerous corps ronds in the basal portion of the greatly hyperkeratotic stratum corneum, hypertrophic dermal villi containing enlarged capillaries, vacuolar dilatation of rough endoplasmic reticulum in sublacunar basal cells, unusually numerous Odland bodies in spinous cells adjacent to lacunae, and persistent attachment of tonofilaments to disrupted desmosomes. Complete separation of tonofilaments from intact desmosomes was not observed. Scanning electron microscopy revealed varied surface morphological appearances of corps ronds and of the epidermal cells covering the elongated dermal villi. The surface cells of cutaneous horns showed little tendency to desquamate.


Cornifying Darier disease--a unique variant. II. Surgical treatment. A case of severe cornifying Darier disease (keratosis follicularis) was successfully treated by deep dermal excision of diseased skin and subsequent dermabrasion, resulting in a remission lasting more than four years to date. Persistent loss of the papillary dermis was observed in the surgically treated, disease-free areas.


Pseudofolliculitis of the legs.

Pseudofolliculitis of the legs. A 19-year-old Iraqi girl had pseudofolliculitis of the legs. Plucking the hair was the initiating factor, and its discontinuation was followed by great improvement. To our knowledge, this is the first report of this entity at this site.


Cutaneous phycomycosis (mucormycosis) with fatal pulmonary dissemination. Phycomycosis of the skin manifested as a spontaneous solitary ulcer of the leg in a patient with uremia. The infection later spread to the lungs and produced fatal pulmonary infarction. Histopathologic study of the lesions revealed broad nonseptate fungal hyphae that had invaded vascular channels, with areas of necrosis and acute inflammation. Primary cutaneous phycomycosis is rare. In the studied cases, dissemination of infection did not occur. The unusual feature of fatal pulmonary dissemination of primary cutaneous phycomycosis as observed in our patient has not been described in the leterature.


Stevens-Johnson syndrome from ophthalmic sulfonamide. A 71-year-old man, who had a history of a previous bullous drug reaction to a sulfonamide, began receiving an ophthalmic preparation that contained sulfacetamide sodium. The patient received only the ophthalmic sulfonamide, and it was used for one day, but he developed Stevens-Johnson syndrome. This is believed to be the first reported case of Stevens-Johnson syndrome caused by an ophthalmic sulfonamide. The sulfonamides are the best verified drug-trigger for erythema multiforme and Stevens-Johnson syndrome.


Linear porokeratosis with giant cornoid lamella. A linear form of porokeratosis, with features that we believe have not been previously described, is presented. The lesions occurred in a dermatome distribution; some of them had a central mass of parakeratotic keratin, shaped like a horn, which we designated a "giant cornoid lamella."


Minocycline hydrochloride treatment for atypical acid-fast infection. Atypical acid-fast infections are not infrequent in the Gulf Coastal region. The development of erythematous papules within three or four weeks after aquatic exposure deserves such consideration. Deeper tissues may also become involved. This should signal a caution when considering the use of corticosteroid injections in such a suspicious lesion. Inasmuch as hypertrophic scar formation at a site of trauma must be considered in the differential diagnosis, it is important to secure histopathologic examination prior to treatment. While a surgical approach has been required for the most part, oral administration of minocycline hydrochloride has brought about healing in the patients reported herein. This article deals with only three cases. However, response was complete and without recurrence in each. Such therapy is recommended prior to the use of more drastic procedures.


Apocrine gland organic hamartoma (apocrine nevus). A patient had two fleshy, nontender masses, each partially filling an axillary vault. These tumors arose at puberty in normal-appearing axillae. The masses were accompanied by localized hyperhidrosis. Histopathological examination of the lesions showed that the reticular layer of the dermis had been replaced solely by lobular masses of unencapsulated, mature apocrine elements. These very rare tumors are best classified as apocrine gland organic hamartomas, or apocrine nevi. To our knowledge, such a case has never been reported or photographed.


Ulcerative colitis and the skin.

Ulcerative colitis and the skin. The association between ulcerative colitis and various abnormalities of the skin, especially pyoderma gangrenosum, has been accepted for many years. The underlying aberrations in either of the organ systems, as well as the basis of their association, however, remain obscure. Several large series of ulcerative colitis patients are reviewed to emphasize the important concomitant cutaneous findings, and investigations into the pathogenesis of pyoderma gangrenosum are discussed.


Incontinentia pigmenti. A world statistical analysis. Incontinentia pigmenti (Bloch-Sulzberger syndrome) is an uncommon genodermatosis that usually affects female infants. I reviewed 464 references from the world literature and found 653 apparently valid reports of patients with incontinentia pigmenti. Skin manifestations were found to be somewhat more common than previously reported, and systemic manifestations were found in 79.8% of the patients.


Microbial degradation of the thiolcarbamate herbicide, diallate, in soils and by pure cultures of soil microorganisms. The disappearance of the herbicide, Avadex (40% diallate), from five agricultural soils (differing in either pH, carbon content, or nitrogen content), incubated under sterile and non-sterile conditions, was followed for a period of 20 weeks. Avadex was rapidly lost from microbiologically active soils, with over 50% of the applied (2.5 ppm) dosage disappearing within four weeks; losses from sterile soils were much slower with recoveries of over 50% after 20 weeks. Incubation of soil with Avadex to which 14C-labeled diallate had been added resulted in rapid formation of 14CO2 from microbiologically active samples and only very slow 14CO2 formation from sterile samples. Substantial quantities of radioactivity were retained as unextractable residues in both sterile and non-sterile soils after senven days incubation. From these data it was concluded that the disappearance of the herbicide from non-sterile soils was mainly due to microbial degradation and to binding of diallate or its metabolites as residues to undefined soil components. Losses from sterile soils were attributed to both binding of residues and to a slow chemical degradation. Avadex degradation by pure cultures was studied using representative fungi isolated from the five soils. Of the fungi tested, Phoma eupyrena, Penicillium janthinellum, and Trichoderma harzianium coudl degrade at least 20% of the applied (2.5 ppm) herbicide after ten days incubation. Degradation of Avadex in soil cultures of T. harzianum was found to be slower than degradation in liquid nutrient cultures.


Comparative studies of instrumental and bioassay methods for the analysis of herbicide residues. A study of the quantitative analysis of herbicide residues by both chemical and bioassay methods in soils is presented. Field and laboratory residue trials were carried out with a representative member of the following groups of herbicides: ureas, triazines, diphenylethers, phenoxyacetic acids, and dithiophosphates. Representative samples were taken at different time intervals, and degradation curves were established both by chemical methods and by two types of bioassay. Chemical analysis either separated active ingredient and metabolites by chromatographic techniques or compresied total residues. Bioassays were performed using either monocotyledons and dicotyledons or algae. The results obtained by chemical and bioassay analysis for the degradation rates of chlorotoluron, ametryn, 2,4-D and C 19490 showed a correlation coefficient of 0.914, indicating that the two methods gave almost identical results. Especially with the highly adsorbed urea and triazine herbicides, the uptake of biologically active material by test plants was slightly less than the solvent-extractable parent compound plus its metabolities, and so the absolute level of residues obtained by bioassay was lower. In the case of fluorodifen, the correlation between the methods was not established. The bioassay showed higher residues and slower degradation than chemical analysis. Various factors which could explain this anomalous result are discussed.


Blue crab mortality: interaction of temperature and DDT residues. Serial observations of DDT-contaminated and uncontaminated salt marshes in the norther Gulf of Mexico were made in November and December, 1973. Blue crab (Callinectes sapidus) mortalities observed in the DDT-contaminated marsh during this period were correlated with reduced daily temperature minima. Gas chromatographic analysis of hepatopancreas and swimmeret muscle tissue of dead and dying crabs revealed total DDT residue concentrations as high as 39.0 ppm and 1.43 ppm, respectively. It is suggested that the DDT body burdens and reduced temperatures interact to produce acutely toxic effects. Several physiological and behavioral mechanisms are proposed.


Translocation, distribution and metabolism of triforine in plants. After short-ter root-treatment of plants with 3H-triforine (labelled in the piperazine ring) or 14C-triforine (labelled in the side chain), the label was translocated primarily to the leaves present at the time of treatment, without any redistribution of the label taking place after termination of the treatment. Autoradiography showed the radioactivity to be very evenly distributed over the leaf blades, without any appreciable accumulation in leaf margins. In infected leaves, however, there was a tendency for increased accumulation at the infection sites. In dilute aqueous solution triforine was decomposed rather rapidly, the chemical half-life being three days only. From these solutions several non-fungitoxic degradtion products have been isolated and their chemical structures determined. In plants, decomposition of triforine was considerably slower than in aqueous solutions, the half-life of the compound varying depending on plant species. In plants, at least four conversion products could be demonstrated, one of which is piperazine. Whether the other three compounds are identical with or structurally related to the breakdown products found in aqueous solution is not yet known. Its low persistence and low animal toxicity suggest that triforine does not offer serious hazards to the environment.


Thermal effects on the accumulation of arsenic in green sunfish, Lepomis cyanellus. The pattern of arsenic concentration in several tissues of Lepomis cyanellus was measured (by neutron activation analysis) as a function of exposure time at 10 degrees, 20 degrees, and 30 degrees C and 0, 30, 60 ppm of arsenic as sodium arsenate. Individual variability of aresenic uptake did not override trends of greater uptake with increasing exposure time, temperature, and arsenic concentration. The mean temperature coefficient of 4.5 for arsenic uptake in livers was higher than O'Hara's (1968) metabolic figures of 1.6 to 3.0 for Lepomis species. The biological half-life of arsenic in liver and gut of live specimens exposed to 30 and 60 ppm of arsenic at 10 degrees C was about one week. Percentage survival decreased and mean arsenic uptake increased slightly as temperature and arsenic concentration increased.


Residue uptake and depletion measurements of dietary oxadiazon in mammalian and avian species. The herbicide oxadiazon, 2-(tert-butyl)-4-(2,4-dichloro-5-isopropyloxy-phenyl)-delta 2-1,3,4-oxadiazoline 5-one, was fed in a total diet at three dosage levels to groups of dairy cows (0.5, 2.5, and 25 ppm) and to groups of male and laying female quail (20, 80, and 160 ppm) for 28 days. Control animals received basal diet rations. No residue (less than 5 ppb) was detected in milk or cream after three days withdrawal from fortified feed. The maximum plateau reached in milk was 83.8 ppb at the highest dosage fed. Tissues of cows sacrificed on the 12th day of withdrawal showed no residue (less than 20 ppb). Birds were sacrified at weekly intervals during acclimation, intake, and withdrawal periods. Eggs were collected at the same intervals. Tissues were free of oxadiazon residue (less than 40 ppb) within two to seven days of returning the quail to the basal ration, and the eggs were residue-free within seven to fourteen days. The maximum residue found in adipose tissue of quail and their fresh eggs was 3100 ppb and 5400 ppb, respectively at the greatly exaggerated dosage of 160 ppm in the diet. A comprehensive analytical methodology, including liquid-liquid partition, absorption chromatography and electron-capture gas chromatography will be discussed.


Effects of the herbicide 2,4-DB and fungicide captan on reactions of mitochondria and chloroplasts. The effects of the herbicide 4(2,4-dichlorophenoxy)butyric acid (2,4-DB) and fungicide N-(trichloromethyltio)-4-cyclohexene-1,2-dicarboximide (captan) on electron transport processes of mitochondria and chloroplasts have been investigated. Chloroplasts, isolated from spinach leaves (Spinacia oleracea L.), were treated with pesticide prior to the addition of electron acceptor and ADP. White potato (Solanum tuberosum L.) mitochondria were either incubated with pesticide before the addition of substrate, or they were treated with pesticide after the addition of substrate and ADP. Captan inhibited oxidation of malate by mitochondria and acted as an uncoupler. With succinate as sunstrate captan was found to stimulate state 4 respiration, as substrate captan was found to stimulate state 4 respiration, with the loss of coupled phosphorylation only at higher concentrations of fungicide. The herbicide 2,4-DB appeared to be 5 to 10 times less effective than captain. Both compounds inhibited phosphrylation-coupled succinate oxidation at higher concentrations and malate-coupled phosphorylation at lower concentrations. They acted as inhibitors of NADH-cytochrome c reductase. Both pesticides inhibited noncyclic electron transport in chloroplasts. The rate of ferricyanide reduction in the presence and absence of phosphorylating agents was reduced, and although the rate of ATP generation was reduced also, the P/2e ratio was not changed much under the influence of pesticides.


Metabolism of ethephon (2-chloroethylphosphonic acid) and related compounds in Hevea brasiliensis. Ethephon (I) is used commercially to prolong the flow of latex from the rubber tree after tapping (Yield stimulation). The compound is applied to the bark in the region of the tapping cut and the effect on latex flow is due to the ethylene released by chemical decomposition, since gaseous ethylene itself is also a very effective stimulant. When 14C-I is applied to the bark of a young Hevea seedling, it is absorbed into the plant by processes which appear to be largely non-metabolic. Ethylene formation commences immediately at the site of application, and the gas is quickly translocated throughout the plant. Translocation of I to all parts of the plant also occurs and the accumulation of 14C in the bark above the zone of application is greater than that below. Chromatographic analysis has shown that compounds other than I remain in the plant tissue. Experiments using 14C-I have shown that detached leaves are able to convert a considerable proportion of the compound to at least twelve non-volatile acid products. One of these is a conjugate of I with an unidentified material. A major component of the products is 2-hydroxyethylphosphonic acid (II), which is itself converted to a number of compounds in leaves. The application of I to bark from mature Hevea, results in the formation of a single substance which is also a conjugate of I. Neither I nor II is effective in inducing the formation of ethylene from endogenous precursors in vegetative Hevea tissue. Ethylene is poorly metabolized by Hevea leaves and the evidence available indicates that it is unlikely that any of the compounds produced from I are metabolites of ethylene.


Human subject experiments to estimate reentry periods for monocrotophos-treated tobacco. Thirteen to fifteen human volunteers worked for eight-hr periods in tobacco fields treated 96, 72, and 48 hr previously with monocrotophos (3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate). At the 48-hr reentry period, during which time no rainfall occurred, both post-exposure plasma and red blood cell cholinesterase levels of the worker group were depressed from pre-exposure levels although the decline was less than 9% in both cases. Rainfall in excess of one inch fell during the 96- and 72-hr reentry intervals, and no important change in cholinesterase levels was noted. Experiments with mice were in general agreement with the human tests. Dimethyl phosphoric acid in urine of the worker group collected prior to, and three hr after, exposure was unchanged in all cases. Rain appeared to have markedly reduced dislodgable residues.


Carcinoma of the ampulla of Vater: Review of 38 cases with emphasis on treatment and prognostic factors. Thirty-eight cases of carcinoma of the ampulla of Vater are presented. The diagnosis has been confirmed at laparatomy in all patients. Three operations were done, a pancreaticoduodenal resection in 23 patients, a biliary-enteric bypass in 7 patients and a biliary-enteric bypass plus excision of tumor in 8 patients. The operative mortality was 8% following resection, 14% following bypass plus excision of the ampulla and 13% following biliary-enteric bypass. Five patients survived 5 or more years. The longest survivors have followed pancreaticoduodenal resections (131 and 216 months). The level of bilirubin or presence of pain did not correlate with prognosis. Prognosis was better in the absence of nodal metastases, and in the presence of papillary tumors.


Staphylococci in community-acquired infections: Increased resistance to penicillin. One hundred patients with community-acquired staphylococcal infections of the skin and soft tissues were treated in the Emergency Ward of Cleveland Metropolitan General Hospital from June to October of 1974. Each staphylococcal infection was considered community-acquired if, within two weeks prior to being treated for the first time, the patient had not received antibiotics, had not been hospitalized, and had not been in contact with other recently hospitalized persons. Of 100 community-acquired staphylococcal infections, 85 were resistant to penicillin. Almost no resistance to other tested antibiotics was observed. Unless indicated otherwise by bacteriologic testing, penicillin is a poor drug of choice in those skin and soft tissue infections suspected of harboring staphylococci.


In vitro penetration of topical antiseptics through eschar of burn patients. The ability of topical antiseptics to penetrate eschar of burn patients was determined by the agar diffusion technique. Gentamicin sulfate, mafenide acetate, nitrofurazone, povidone-iodine, silver nitrate, and silver sulfadiazine were tested against clinical isolates of Candida albicans, Staphylococcus, Streptococcus, and gram-negative bacilli including Pseudomonas aeruginosa. In practically all instances, the diameters of the zones of inhibition observed using eschar were comparable to those obtained with filter-paper discs. This finding showed that the antimicrobial agents could penetrate eschar and retain their effectiveness after penetration.


The effect of acute popliteal venous interruption. Popliteal vascular trauma continues to be associated with a relatively high morbidity rate when compared to other major vascular injuries in extremities. There is continuing controversy regarding the management of popliteal venous injuries. The advocates of ligation of injured veins have postulated that there is an increased incidence in thrombophlebitis and pulmonary embolism associated with attempted venous repair. There is a paucity of valid statistics supporting either side of this controversy. Clinical experience documented in the Vietnam Vascular Registry and experimental work at Walter Reed Army Institute of Research have supported our more aggressive approach for venous repair. This study evaluates the management of 110 injured popliteal veins without associated popliteal arterial trauma. Nearly an equal number were ligated and repaired. Thrombophlebitis and pulmonary embolism were not significant complications in this series. The only pulmonary embolus occurred after ligation of an injured popliteal vein. However, there was a significant increase in edema of the involved extremity following ligation, 50.9% compared to 13.2% after repair.


Penetrating cardiac wounds: A comparison of different therapeutic methods. The management of penetrating wounds of the heart has been controversial. During the last 10 years we have used 3 different therapeutic approaches for the treatment of these wounds and the obtained results comprise this report. From 1964 to 1974 we treated 102 patients, four of whom expired immediately after their arrival to the clinic. The remaining 98 patients were divided into five groups according to their clinical presentation and treatment. Group I, 17 patients (14 with stab and 3 with bullet wound) seen with cardiac tamponade from 1964 to 1967 were treated first with pericardiocentesis and then were operated upon if pericardiocentesis yielded no results or if cardiac tamponade recurred. Fourteen patients recovered and three died, with an overall mortality of 17.5% Group II, 34 patients (23 with stab and 11 with bullet wound) were seen with cardiac tamponade from 1968 to 1971. The patients with stab wound were managed the same as group I patients and those with bullet wound were operated upon immediately. Twenty-nine recovered and 5 died, with an overall mortality of 14.7%. Group III, 20 patients (12 with stab and 8 with bullet wound) were seen with cardiac tamponade from 1972 to 1974. All of them were operated upon immediately and pericardiocentesis was used in this group only to provide time for a safe operation. Nineteen recovered and one died, with an overall mortality of 5%. Group IV, 20 patients (5 with stab and 15 with bullet wound) with massive bleeding, were operated upon immediately. Ten (4 out of the 5 with stab and 6 out of the 15 with bullet wound) recovered, with a mortality rate of 50%. Group V, seven patients were seen throughout the study period without bleeding or cardiac tamponade. Some of them were operated upon electively and others are being followed and all have done well. This study suggests (1) that patients with penetrating wound of the heart and cardiac tamponade or bleeding will derive better results if they are operated upon as soon as possible and if pericardiocentesis is used to provide time for a safe operation and (2) that those with other manifestations should be evaluated and if their lesion is significant, they should be operated upon electively.


L-dopa in hepatic coma.

L-dopa in hepatic coma. The use of L-Dopa in hepatic coma has been the subject of numerous reports since 1970. The following represents our experience with a rather heterogenous group of patients treated at the Massachusetts General Hospital over the past 4 years. Thirty-five patients with severe liver disease, a mean age of 53 +/- 3.5 years, including nutritional cirrhosis with acute coma and acute hepatitis were treated. Four patients were judged grade III, 31 patients grade IV. All patients had previously been treated with protein restriction, orally administered non-absorbable antibiotics, fluid and electrolytes, and in some cases, steroids. L-Dopa was given orally in 21 patients, and as a retention enema in 14. Thirteen of the 35 patients did not respond to therapy. Seventeen responded, but did not survive, and 5 patients responded and survived. There was no difference between any of the groups as far as dosage of L-Dopa and clinical features. The one striking finding as the differences between groups was the time of initiation of L-Dopa therapy. In Group I, the survivors, therapy was started within 1.4 +/- 0.8 days after the onset of coma. In Group II, there was an initiation of therapy at 6.7 +/- 1.6 days, and in the non-responders 9.5 +/- 1.6 days. These differences are highly significant. The results suggest that coma may pass from a reversible to an irreversible stage, and that L-Dopa therapy initiated early in the course of hepatic coma, may be of some benefit.