Temporomandibular joint disk displacement without reduction. Treatment with flat occlusal splint versus no treatment. A flat occlusal splint has been extensively used in the treatment of patients with temporomandibular joint disk displacement without reduction, but no studies with untreated controls have assessed its effect. We randomly assigned 51 patients with temporomandibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial. Pain symptoms disappeared in about one third of the patients in each group. Another third of the patients in the control group improved. Sixteen percent of the patients in the control group and 40% of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study. Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group. A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction. The use of a flat occlusal splint in this patient group should therefore be reconsidered.


The morbidity associated with fifty maxillary fractures treated by closed reduction. Fifty patients with maxillary fractures treated by closed reduction over an 85 month period at a Level I trauma center were reviewed. Thirty patients (60%) experienced forty-one midfacial complications. The most frequent problems were infraorbital nerve paresthesia (12), enophthalmus (5), septal deviation (3), and altered vision (3). No relationship could be established between complications and age, sex, cause of injury, or the method of suspension used. Most complications were related to concomitant injury or the concurrent management of fractures of other facial bones. Only eight problems (16%) were directly attributed to the closed reduction of maxillary fractures. Patients treated by closed reduction and maxillomandibular fixation without suspension experienced no surgical complications.


Maxillary osteomyelitis and spontaneous tooth exfoliation after herpes zoster. Reports of spontaneous tooth exfoliation and osteonecrosis trigeminal herpes zoster are extremely rare and have been sporadic. This article reports a pertinent case of a 50-year-old man who exhibited prodromal odontalgia before the appearance of vesicular mucocutaneous lesions, together with severe destruction of the maxillary bone and exfoliation of multiple teeth. This patient was successfully treated using a unique closed nasal-vestibular drainage system for the ultimate control of maxillary bone viability. A review and analysis of the clinical aspects and the pathogenesis of herpes zoster and bone necrosis are discussed.


Traumatically induced peripheral osteoma. Report of a case. Osteomas of the jaws are well-defined lesions that can present as an isolated finding or as part of a syndrome (e.g., Gardner's syndrome). The etiology of peripheral osteomas is somewhat controversial. Trauma has been implicated by several authors, and osteoma is presented here as a rather striking lesion with well-defined traumatic origins.


Effects of total body irradiation on salivary gland function and caries-associated oral microflora in bone marrow transplant patients. Forty-one cancer patients who received chemoradiotherapy conditioning with bone marrow transplantation were examined for changes in salivary gland function and caries-associated oral microflora. Salivary flow rates (stimulated and unstimulated) and Streptococcus mutans levels decreased after pretransplant cytoreductive therapy and posttransplant prophylactic antibiotic therapy. Normal levels returned with time after the patients left the protected environment. Lactobacillus counts were not affected. Chronic graft-versus-host disease did not significantly influence saliva production. Results indicate that irradiation is probably the major factor responsible for the transient xerostomia.


Blood pressure response to routine restorative dental treatment with and without local anesthesia. Continuous noninvasive blood pressure registration with a finger manometer. A continuous noninvasive blood pressure registration with the Finapres finger manometer was carried out during routine dental treatment, with and without local anesthesia. Forty patients (21 male), 21 to 64 years of age, were studied. Blood pressure was recorded continuously from 10 minutes before dental treatment to 10 minutes after treatment was completed. No local anesthetic was used in 25 patients. In 15 patients (seven men) local anesthetic was used. All patients showed a considerable blood pressure variation. During treatment a significant mean blood pressure increase was registered in the patients treated without local anesthesia. In the patients treated with local anesthesia no significant mean blood pressure changes during dental treatment could be established. However, during the actual administration of the local anesthetic solution a transient blood pressure increase was found, followed by a decrease shortly after removal of the needle from the mouth. After treatment of both groups of patients, a mean blood pressure decrease was established.


Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation. The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers. The current randomized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine, nystatin, and saline solution rinses to reduce the findings of oral mucositis, gingivitis, and oral infection. The results of this study did not show a reduction in mucositis with the use of these rinses. However, potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse.


Plasma cell gingivitis. Report of two cases. Plasma cell gingivitis is a disorder first described in the 1960s and was believed to be caused by an allergic reaction to flavored chewing gum and toothpaste. The lesion was believed to have been largely eliminated by removing the allergens from the products. We report two additional cases, not related to a known allergen. One patient was allergy tested thoroughly and given a strict elimination diet without resolution. Immunofluorescence study suggests a reactive rather than a neoplastic process.


Immediate biopsy versus a therapeutic trial in the diagnosis and treatment of vesiculobullous/vesiculoerosive oral lesions. Opposing viewpoints presented. There are at least two treatment strategies in the diagnosis and treatment of oral vesiculobullous/vesiculoerosive disease. The relative merits of immediate biopsy and initial therapeutic trial regimens are debated.


Lichenoid lesions of oral mucosa. Diagnostic criteria and their importance in the alleged relationship to oral cancer. Lichen planus and other lichenoid disorders of oral mucosa occur commonly, and yet they are poorly understood. Further, the question of the premalignant potential of oral lichen planus remains deeply mired in controversy. The object of this article is to delineate these problems, clarify the issues, and present evidence to support the position that true lichen planus of oral mucosa is not only less common than generally appreciated but also has no inherent predisposition to become malignant. Rationale and data from the literature are offered in support of this position.


Cinnamon-induced stomatitis venenata, Clinical and characteristic histopathologic features. Fourteen new cases of cinnamon-induced stomatitis are reported. Ten of these fourteen cases were first detected on the basis of histopathologic changes, which included hyperkeratosis, chronic lichenoid mucositis with plasmacytic infiltration, and marked chronic perivasculitis. Six cases of false-positive histopathologic findings are presented for comparison. It is recommended that when the histopathologic features described are recognized, cinnamon stomatitis should be considered.


Survey of tissue diagnostic services in U.S. dental schools - 1990. Tissue diagnostic services in U.S. dental schools were surveyed to determine activities during 1990. Results were compared with those of similar surveys conducted in 1953, 1958, 1969, 1975, 1980, and 1985. The information gathered from this survey reveals a progressive growth and development of tissue diagnostic services. This is seen not only in the increased numbers of biopsy accessions, which increased by 37% since the last survey, but is also reflected in the diversity of services now offered by oral pathologists.


Oral Geotrichum candidum infection associated with HIV infection. A case report. Infections with Geotrichum species, although rare, are sometimes seen in immunocompromised hosts. We report a case of oral geotrichosis in a patient seropositive for human immunodeficiency virus who had erythematous mandibular and maxillary gingiva but was otherwise free of any active systemic disease. Geotrichum candidum was shown by both culture and histopathology to be present in the lesion and was deduced to be the causative organism. The patient responded well to several weeks of treatment involving oral topical administration of nystatin vaginal tablets.


Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review. Eugenol-containing dental materials are frequently used in clinical dentistry. When zinc oxide-eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol diffuse through the dentin to the pulp. Low concentrations of eugenol exert anti-inflammatory and local anesthetic effects on the dental pulp. Thus use of ZOE temporary filling may facilitate pulpal healing; on the other hand, high eugenol concentrations are cytotoxic. Direct application of eugenol to pulp tissue may result in extensive tissue damage. The ability of ZOE-based endodontic sealers to influence periapical tissue healing is considered in view of eugenol's anti-inflammatory and toxic properties.


Biocompatibility of retrograde filling materials in the ferret canine. Amalgam and IRM. Periapical tissue response to retrograde fillings of amalgam and IRM were compared in the mandibular canine of the adult male ferret. Teeth were cleaned and shaped with a standard technique and obturated with gutta-percha. The root apex was then exposed and retrofillings were placed. The animals were grouped according to observation periods of 5, 10, and 15 weeks. At the proper time the animals were killed and the lower canine tooth along with the surrounding bone was removed. The tissue blocks were examined clinically, radiographed, and prepared for histologic examination. The clinical and radiographic examination indicated both materials to be well tolerated by periapical tissues. Microscopic examination of amalgam specimens showed a decrease in inflammation and the formation of a fibrous capsule over the 15-week period. IRM specimens showed persistent inflammation and slower healing potential.


Diagnosing periapical bone lesions on radiographs by means of texture analysis. Trabecular pattern, the radiographic projection of trabecular bone, is a repeated structure that appears in a dental radiograph. Texture analysis, the computer image analysis of repeated patterns, is a technique that can be used to automate the diagnosis of periapical lesions with the detection of the absence of the texture that corresponds to the trabecular bone. The purpose of this study was to determine whether it is feasible to use texture analysis to identify the presence of the trabecular pattern in radiographs and to detect a periapical bone lesion based on a local absence of this pattern. Thirty-two mandibular periapical films, 16 with and 16 without periapical lesions, were used in this study. Texture analysis was carried out on the digital images of these radiographs. In the 16 films with lesions, they were all correctly identified, and no lesions were found in the 16 films without lesions. This result is based on the a prior knowledge of the user about the localization of the disease. Locating periapical regions without user interaction is a goal for future research.


Quantitative features of digitized radiographic bone profiles. The purpose of this investigation was to examine the use of four image features in describing digitized radiographic bony scan lines, or profiles. These features include the mean pixel intensity, I (x); pixel intensity variance, var I (x); mean absolute Fourier transform coefficient, magnitude of F(u); and mean spatial first moment of the absolute Fourier coefficients, M1. In an animal model I (x) and M1 differed significantly while magnitude of F(u) tended to differ significantly between digitized radiographic profiles of osteoporotic (n = 6) and control (n = 6) rabbit humeri. Case examples illustrating the application of this technique to digitized radiographs of human interproximal alveolar bone are presented.


Cementoblastoma in Hong Kong Chinese. A report of four cases. Four cases of cementoblastomas in Hong Kong Chinese are presented, two are classic lesions and two are clinically and radiologically atypical. A summary of the literature is presented in tabular form.


Pulse oximetry during minor oral surgery with and without intravenous sedation. This study investigated the levels of oxygen saturation and pulse rates of patients undergoing minor oral surgery under local analgesia, with (20 patients) or without (20 patients) intravenous sedation with midazolam. The results indicated that a statistically significant fall in arterial blood oxygenation of 1% to 2%, as measured by pulse oximetry, followed midazolam administration; however, this was physiologically insignificant. Both groups showed a similar postoperative small fall in oxygen saturation. Transient episodes (24 to 36 seconds) of physiologically significant mild hypoxia occurred during breath holding, but this condition was readily corrected by encouraging patients to breathe deeply. Midazolam had a small but significant calming effect on the higher preoperative pulse rates exhibited by anxious patients, but this effect was not sustained during the operating period. Both sedated and unsedated patients showed episodes of tachycardia that could have significance for patients with cardiac disease.


Hypoglycemia as a possible factor in the induction of vasovagal syncope. Glucose level was estimated in capillary blood of 16 patients, who had vasovagal syncope during exodontia with local anaesthesia. One consistent finding was the low blood sugar level in all patients during syncope, as compared with the level 1 hour after recovery. Hypoglycemia can be induced by parasympathetic activation; this may be the product of reflex conditioning. Modest lowering of blood sugar levels can also act in synergy with hypotension and hypocapnea to induce loss of consciousness. Psychogenic syncope may be mediated through a mechanism involving hypoglycemia. Reflex conditioning perhaps accounts for the small but consistent fraction of the adult population who have repeated fainting episodes.


Recurrence of a solitary bone cyst of the mandibular condyle in a bone graft. A case report. The recurrence of a solitary bone cyst of the mandibular condyle in a costochondral bone graft is reported. A solitary bone cyst of the right condylar head and neck of a 10-year-old boy was treated by total resection and immediate reconstruction with a costochondral bone graft. Two years after the first operation, a recurrence of the solitary bone cyst within the bone graft was noted. An open treatment was performed. A review of the literature on solitary bone cysts and recurrences of solitary bone cysts shows that the case reported is unique. Possible reasons for the recurrence are discussed.


Diffuse sclerosing osteomyelitis (chronic tendoperiostitis) of the mandible. An 11-year follow-up report. Diffuse sclerosing osteomyelitis of the mandible is a disease that is characterized by a protracted course of recurrent pain, swelling of the cheek, and trismus. The cause of the lesion has been obscure for a long period of time. Recent research, however, pointed out that this disease is likely to be caused by overuse of the jaw musculature (chronic tendoperiostitis) and can be treated accordingly. The protracted course of the disease and the difficulty of treatment with an eventual positive outcome are illustrated by a case report of a 65-year-old man with an 11-year history of diffuse sclerosing osteomyelitis (chronic tendoperiostitis) of the mandible.


Bronchogenic metastasis to the gingiva.

Bronchogenic metastasis to the gingiva. We report a rare case of a bronchogenic adenocarcinoma metastatic to the lower gingiva as the first clinical sign of metastatic disease. The following safe approach is recommended: a tumor in the oral cavity should be regarded as malignant or as a metastasis until the hypothesis can be abandoned.


Comparative trial of oral clotrimazole and nystatin for oropharyngeal candidiasis prophylaxis in orthotopic liver transplant patients. A prospective randomized study was conducted to assess the effectiveness of clotrimazole troches and nystatin suspension to prevent oral candidiasis in immunosuppressed orthotopic liver transplant patients. Thirty-four patients received either clotrimazole troches, 10 mg, five times daily, or nystatin suspension, 500,000 units, four times daily. Prophylaxis was initiated after extubation after transplantation and continued throughout the hospitalization. One of 17 patients in each treatment group developed clinical and microscopic evidence of an oropharyngeal Candida infection. This gave an intragroup and an overall infection rate of 5.9%. It appears that either nystatin or clotrimazole may be used for candidiasis prophylaxis in orthotopic liver transplant patients.


Clinical evaluation of fifty-six patients referred with symptoms tentatively related to allergic contact stomatitis. During a 7-year period, 56 patients were referred to the Department of General Pathology and Internal Medicine and the Department of Dental Materials, University of Amsterdam, to determine whether contact allergic reactions to dental materials were the cause of their complaints. On the first consultation with the patient a detailed history focusing on the complaints themselves, general medical history, and special clinical history of allergic skin reaction was obtained. Oral examinations were performed, and all patients were referred to the allergy clinic at the department of dermatology for skin tests. There was a strong female predominance in the referred group. Most of the patients with allergic contact stomatitis mentioned a burning sensation in the mouth. In only 16 of the 56 patients could the diagnosis of allergic contact stomatitis be established. From this study it can also be concluded that the combination of a positive allergic history and positive allergic skin reactions with or without visible oral signs are important for the diagnosis of allergic contact stomatitis.


Familial ogee roots, tooth mobility, oligodontia, and microdontia. The term ogee is proposed to describe dome or onion-shaped incisor roots as presented in a family study. A case of ogee permanent upper incisor teeth associated with microdontia, oligodontia, and tooth mobility is described. Forty-seven members of the proband's family were examined. The dental abnormalities were found to be of an autosomal dominant pattern of inheritance.


Necrosis of the tongue in a patient with intestinal infarction. A patient with a rare combination of bilateral lingual necrosis and intestinal infarction, caused by giant cell arteritis, is described and the literature reviewed.


Orofacial manifestations of Melkersson-Rosenthal syndrome. A study of 42 patients and review of 220 cases from the literature. We investigated orofacial manifestations in 42 patients with Melkersson-Rosenthal syndrome who were examined at our institution between 1965 and 1990. Patient histories and histologic and clinical findings were reviewed in detail. These data were compared with the oral findings in 220 cases that were reported in the literature between 1965 and 1990. There were 28 females in our study. The age at onset of signs and symptoms varied widely with a mean of 33.8 years. Most frequent initial signs were labial edema, facial swelling, and Bell's palsy. During the course of the disease, 75% of all patients had labial swelling, 50% had facial edema, and 33% had Bell's palsy. Swelling, erythema, or painful erosions that affected the gingiva, buccal mucosa, palate, or tongue were common intraoral symptoms. A comparison with patients reported in the literature revealed a similar frequency of extraoral symptoms but more prevalent intraoral symptoms in our patients.


Oral congenital dermoid cyst in the floor of the mouth of a newborn. The significance of gastrointestinal-type epithelium. A case of congenital dermoid cyst in the floor of the mouth in a newborn is presented. The presence of microcyst formation with intestinal-type epithelial lining and mucin histochemistry are discussed.


Oral caliber-persistent artery. Unusual presentations of unusual lesions. Two cases of oral caliber-persistent artery are reported. Both cases were different from the five previously reported oral examples of this unusual entity. One case is the first reported instance of a caliber-persistent artery not associated with spontaneous hemorrhage, inflammation, or ulceration. The clinical importance of this entity to the patient and the treating practitioner is stressed.


Bacterial microleakage of Cavit, IRM, and TERM. In this in vitro study, a model system was developed and tested to evaluate the sealing ability of temporary restorative materials used in endodontic access preparations. The materials studied, Cavit, IRM, and TERM, were tested on 40 premolars against a known bacterial species, Streptococcus sanguis. The leakage of bacterial cells was checked 4 and 8 days after initial immersion in the culture. Thermocycling was introduced on the fourth day. After 8 days the cement thicknesses were measured after the teeth had been longitudinally sectioned. Before and after thermocycling, IRM was less leakproof than Cavit (p < 0.05) and TERM (p < 0.05). Thermocycling aggravated percolation in the case of IRM, and decreased the tightness of Cavit, whereas TERM remained leakproof. The thicknesses were as follows: Cavit, 3.73 mm; IRM, 3.45 mm; and TERM, 5.49 mm. There was no statistically significant relationship between thickness and tightness.


Coronal dye penetration of the apical filling materials after post space preparation. Forty canals of palatal and distal roots of molars were cleaned and shaped with the use of a step-back technique. Thirty canals were obturated, 10 each with lateral, vertical, and thermafil techniques. Five root canals were obturated without a root canal sealer and served as positive controls. Another five root canals were obturated, and their coronal half was sealed with sticky wax and served as negative controls. The apical 5 to 6 mm of the filling materials were exposed to india ink for 48 hours. The depth of dye penetration was measured in all groups and statistically analyzed. The apical plugs in the thermafil group had the highest degree of coronal leakage. The ANOVA test showed a significant statistical difference between coronal dye leakage between this group and those found in canals filled by lateral or vertical condensation techniques. The results indicate that the apical filling materials obtained by lateral or vertical condensation leak less than those obtained by thermafil.


Complement activation by lipopolysaccharides purified from gram-negative bacteria isolated from infected root canals. The purpose of the present study was to investigate the complement activation by lipopolysaccharides purified from Porphyromonas (Bacteroides) endodontalis, Veillonella parvula, and Fusobacterium nucleatum isolated from infected root canals. The rate of consumption of the C3T component of the complement increased remarkably when lipopolysaccharides of more than 10 micrograms were added.


Direct digital radiography for the detection of periodontal bone lesions. In this study the diagnostic accuracy of D-speed and E-speed film in the detection of simulated periodontal bone lesions was compared with that of an electronic direct digital image receptor. Lesions of increasing depth were created in 11 human hemimandibles at the buccal cortical plate in the interproximal marginal bone area by means of 1.4 mm diameter round bursa. Specimens were imaged at each lesion stage with the use of all three receptors. Nine viewers used a 5-point rating scale to evaluate whether lesions were present or absent in the resulting images. Receiver operating characteristic curves were generated, and maximum-likelihood curve areas were calculated. The area under the curve was used as the index of diagnostic accuracy. The mean receiver operating characteristic areas for D-speed film, E-speed film, and the direct digital system were 0.745 +/- 0.038, 0.740 +/- 0.038, and 0.741 +/- 0.037, respectively. Critical ratio analysis was used to compare the means. No statistical difference was found between any of the three image receptors (p > 0.05) for the detection of simulated periodontal lesions 1.0 to 3.0 mm in depth, which suggested that the digital system performed comparably with conventional film systems.


Radiographic demonstration of oronasal fistulas in patients with cleft palate with the use of barium sulfate contrast. The purpose of this investigation was to determine the overlapping and unique contributions that radiographic techniques might provide for accurate characterization of hard palate fistulas associated with cleft palate. Five subjects with oronasal fistulas were selected for radiographic imaging, and their informed consent was obtained. Results indicated that radiographs with contrast can provide important supplemental and unique information. Qualitative descriptions of the inferior-superior course and location, and the size of the narrowest aperture could be obtained from the combination of maxillary occlusal, posteroanterior tomographic, and lateral tomographic projections. This information could not be obtained from the common clinical methods in use to describe fistulas. This technique can provide valuable information to all members of a multidisciplinary cleft palate team to document palatal fistulas for both clinical and research purposes.


Winchester syndrome. A case report and literature review. The mucopolysaccharidoses are a group of inherited lysosomal storage diseases that are caused by a deficiency of specific enzymes. The acid mucopolysaccharides are stored in tissue and excreted in large quantities in the urine. The storage of this material leads to effects on a wide variety of tissues and to remarkable changes in morphologic features. Winchester syndrome is a rare disorder in the group of mucopolysaccharidoses. This article is a report of a case with classic clinical, radiologic, and biochemical characteristics of the Winchester syndrome.


Contraindications to vasoconstrictors in dentistry: Part I. Cardiovascular diseases. This article reviews the main contraindications of vasoconstrictors in cardiac patients, notably unstable angina, recent myocardial infarction, recent coronary artery bypass surgery, refractory arrhythmias, untreated or uncontrolled hypertension, and untreated or uncontrolled congestive heart failure. Extensive survey of the literature has been completed, giving specific guidelines for a rational use of vasoconstrictors in this category of medically compromised patients.


Contraindications to vasoconstrictors in dentistry: Part II. Hyperthyroidism, diabetes, sulfite sensitivity, cortico-dependent asthma, and pheochromocytoma. Dentists are aware of contraindications to the use of vasoconstrictors in patients with cardiovascular diseases. However, there are some other noncardiac conditions we should know. This article discusses the absolute contraindications to the use of vasoconstrictors in patients with a history of hyperthyroidism, diabetes, allergy to sulfites, asthma, and pheochromocytoma.


Intraoral vesicles occurring after alginate impressions. In 47 of 227 dental students intraoral vesicles developed after multiple alginate impressions. The lesions were generally solitary and clear, and appeared within 24 to 48 hours after the impression. They were most frequently located inside the vermilion border of the lips and resolved spontaneously in 2 to 5 days. The purpose of this study was to determine the cause of these reactions. Histopathologically one lesion was suggestive of a contact allergy. Cutaneous patch tests, which proved negative, were performed on 14 students to determine whether an allergy to the alginate flavoring existed. The surface of three lesions were cultured and the organisms identified. Contamination studies were carried out on seven unopened containers of the alginate powder and resulted in the isolation of some organisms similar to the mucosal cultures; however, no relationship can be proved. These findings indicate that the cause of the vesicles remains unknown, and further studies are necessary to establish the cause.


An initial assessment of the Veterans Affairs occurrence screening program. The Department of Veterans Affairs (VA) established a computerized occurrence screening program in its medical centers in October 1988. Data collected from these hospitals suggest that occurrence screening has been a useful component of the VA's overall quality assurance effort; opportunities for improvement were found in 4.2% of all occurrences. When asked to name the three most effective criteria, there was strong agreement among participating hospitals--50% or more of the facilities ranked readmissions, death, and admission within three days of an unscheduled outpatient visit as the most effective. A majority of facilities (56%) named occurrence screening as one of the more effective elements in identifying quality-of-care issues. These findings must be balanced against important limitations of the occurrence screening process; however, guided by the data it collected, the VA has recently made several changes in its occurrence screening program to address these limitations.


Lessons learned from an early attempt to implement CQI principles in a regulatory system. This article describes the Quality Assurance Project (1978-1982), which was developed as a demonstration project by a Wisconsin research team and was intended to implement and evaluate new methods for carrying out the regulatory roles of facility and resident assessment in Wisconsin nursing homes. The new method included (1) a screening process to distribute efforts between sanctioning and process improvement, (2) role changes that would move surveyors beyond problem identification toward education and consultation, and (3) a resident review process based on efforts to find systems-level problems. For the first three years of the project (reported here) certain principles were followed, many of which were similar to those of continuous quality improvement (CQI). Although this is an imperfect example of CQI implementation in a regulatory organization, it contains important lessons that may be helpful in integrating the CQI philosophy into other external review efforts.


New methods for evaluating utilization management programs. Blue Cross and Blue Shield of Massachusetts, Inc (BCBS), has developed two new methods for measuring the effect of utilization management (UM) in reducing unnecessary hospital use. The "program component" method measures the separate effect of preadmission review, concurrent review, and discharge planning. The "savable days" method produces a composite measure of the effectiveness of the program as a whole. The use of these two methods is illustrated with five years of utilization review data from the BCBS nongroup insurance product. The results can be used by operations managers and policymakers to measure the performance of individual UM components and the program as a whole, to establish goals and monitor program performance, to modify the program in response to changing utilization patterns, to assist in developing premiums, to establish risk-sharing agreements with employers or providers, and to demonstrate the effectiveness of the program for use in marketing.


A patient transport pilot quality improvement team. The transportation of inpatients within the hospital is a critical component of the patient care process. A quality improvement (QI) team at Massachusetts General Hospital (Boston) convened to improve this process and to pilot the QI approach there. Pilot QI projects have the burden of intense scrutiny by senior management at a point when the fundamentals needed for a successful QI project are scarce or not yet available. The authors, who were participants in this project, describe the methodology and outcomes of this pilot QI process as well as the lessons learned. The results confirm that, although difficult, it is possible to succeed in pilot projects and gain the support needed to move on to the next step in the QI journey.


Review of medical care in cited nursing homes: key areas of deficiency. This article identifies key areas of physician performance in nursing homes (NHs) cited by state regulators. Six faculty members of the University of Maryland Department of Family Medicine reviewed medical care in ten Maryland NHs, which constituted 6.7% of Maryland's Comprehensive-level beds, with a sample of 547 charts and 81 physicians. The reviewers recorded the absence of expected minimum standards of performance in patient care. Nine of the NHs had been cited and one was anticipating an audit by state regulators. Citation by regulators corresponded with inadequate documentation of patient history and physical examinations, especially of neurologic conditions; with inadequate health care maintenance; with mismanagement of laboratory findings such as bacteriuria; and with lack of medical administrative leadership and quality management. These key areas of physician performance should be regularly assessed or systematically changed in all NHs to maintain at least minimum standards of care.


Continuous quality improvement of Pap smears in an ambulatory care facility. This article describes how the H. Claude Hudson Comprehensive Health Center (Los Angeles) implemented a continuous quality improvement program to reduce the unacceptably high rate of nonrepresentative Papanicolaou (Pap) smears (those lacking endocervical component). A review of the literature and telephone surveys indicated that the optimal Pap smear technique includes the use of a cervical cytobrush. Several cytobrushes were evaluated and one was chosen to be used facilitywide. Clinicians were given in-services on the proper cervical sampling techniques using the cytobrush. The rate of nonrepresentative Pap smears decreased approximately 12% during a five-month period; this has been attributed to uniform implementation of the cytobrush technique in nonpregnant patients, in-service education, and cooperative teamwork.


Integrating total quality management and quality assurance at the University of Michigan Medical Center. Staff members from the University of Michigan Medical Center (UMMC), 1990 winner of the Commitment to Quality Award, describe how they integrated its quality assurance (QA) program into its total quality management (TQM) strategy. The QA program has changed in recent years to establish quality as a central priority, to educate staff in the importance of quality, and to disseminate information more effectively. While these initiatives were underway, UMMC began to embrace TQM as an operating philosophy. Recognizing both the strengths and weaknesses of QA, staff members have worked to apply TQM principles (eg, focus on processes) to QA while using the ongoing monitoring of QA to identify opportunities for improvement within the organization's TQM management system.


The financial benefits of an effective hospitalwide quality assurance/utilization management program. This article describes the organizational structure and functions of the quality assurance/utilization management (QA/UM) department at The Johns Hopkins Hospital (Baltimore), which has developed a proactive QA/UM program for identifying opportunities to control inappropriate inpatient admissions, shorten a patient's length of stay, monitor the use of ancillary services, and improve physician documentation in patient medical records. In addition, the QA/UM department has developed and implemented an aggressive third-party appeal mechanism to ensure that the institution has an effective UM program. The QA/UM department annually recovers more than 3 million dollars for the hospital by aggressively appealing third-party payer denials. Specific chart-review variables are outlined.


The development of quality assurance in the German health care system. Quality assurance efforts in the German health care system have primarily been a responsibility of the medical profession. The Federal and State Physician Chambers coordinated early quality assurance studies, which conformed to the guidelines of voluntary participation by physicians, confidentiality of data, and no imposition of sanctions for poor performance. These guidelines were challenged by the Health Reform Act of 1989, which made the legal regulations for quality assurance the same for hospitals as for out-patient care. Some current draft implementation plans conform to the principle of anonymity, requiring no disclosure of patient-specific, physician-specific, or hospital-specific data to third parties; others allow release of data to individual insurers or their associations. Although no consensus has been reached as to how quality assurance will be performed in the future in Germany, it will clearly become an integral part of the system.


The physician and employee judgment system: reliability and validity of a hospital quality measurement method. Hospitals engaged in quality improvement must measure and assess customer perceptions of hospital services. Hospital customers are either "external"--patients, their families, and payers--or "internal"--physicians and hospital employees. This article describes two measurement systems designed to gather information from internal customers about the quality of hospital services. One system targets physicians, the other hospital employees. This article describes how these systems were developed and pilot-tested, and how the results were analyzed. Analysis of results showed the systems to be reliable, valid, and representative. The article also addresses limitations of the research (focus on general acute-care hospitals), interesting findings and implications (the correlation between physicians' and employees' ratings of hospital quality), and uses of these measures in corporate-level and hospital-level quality improvement (measuring trends and identifying specific opportunities for improvement).


Total quality management in a 300-bed community hospital: the quality improvement process translated to health care. Winter Park Memorial Hospital (Winter Park, Florida) began implementation of a well-strategized plan for total quality management (TQM) in 1987. Having no guidelines for applying TQM to health care but using the industrial quality management techniques of Philip Crosby Associates, Inc, the hospital made the transition and saved thousands of dollars in the process. This article describes the transition, especially the integral part played by the Medical Staff Quality Council in changing the hospital's culture.


Integrating external clinical information with the ten-step monitoring and evaluation process: from theory to practice. Traditionally, Sisters of Mercy Health System (SMHS)-St Louis hospitals have had difficulty integrating quality information from external sources into their own monitoring and evaluation activities. This difficulty became apparent at the 14 hospitals of the SMHS when the system headquarters began providing its hospitals with comparative clinical outcome information. Although the hospitals found value in the comparative studies, the information was not fully used in individual hospitals' quality improvement efforts. As a result, SMHS developed a model for integrating external quality information into the local hospitals' ten-step monitoring and evaluation process. This article explains the integration model and shows how it has worked in several clinical scenarios.


[Transcranial Doppler sonographic study of the effect of electroconvulsive therapy on the circulation in the median cerebral artery]. The authors monitored the circulation of middle cerebral artery in subdominant hemisphere using the transcranial Doppler sonographic method during electroconvulsive treatment. They intravenously administered the patient 500 mg propanididum to put him/her to sleep and 150 mg of suxamethonium for muscle relaxation. The phasis of narcosis and awakening were continuously recorded under the treatment. After the administration of propanididum a sudden brief rise in flow velocity was measured with transient bradycardia followed by tachycardia. After the muscle relaxation the peak flow velocity diminished long lasting and the mean flow velocity fell from 60 cm per second to 30 cm per second average. At the beginning of the electroconvulsive treatment the velocity suddenly rose. The flow velocity increased significantly during the clonic phase of convulsive jerks with the pulsatility indices falling rapidly. Very low pulsatility indices lasted for long period of time during and following clonic convulsions.


[Significance of leukocytes and bacteria in the gastric aspirate from neonates]. The cytological pictures of the gastric aspirates of 2582 newborns were evaluated by a semiquantitative method. A high number of germs was found in the majority of the early onset sepsis and pneumonia (19/22). In the late onset and local connatal infections were found no significant cytological abnormalities. A high number of germs was a rare finding in the healthy newborn population (11/2456).


[Duplex ultrasound scanning of the carotid arteries in patients with obliterative diseases of the lower extremities]. The authors practiced carotis duplex scanning examinations on 60 patients having lower limb artery disease. The patients were grouped according to, having cervical bruit or not. In the first group 100% had stenosis while in the second group had only 13.3%. Furthermore the stenosis--plack were analysed according to the severity of the lower limb artery disease. The severity of stenosis can be found in group "A" (bruit exists) and group "B" (no bruit) accordingly to the Fontaine stages. Stenosis higher then 50% was found in group "A" 3 in Fontaine stage II, and 10 in Fontaine stage III. While in group "B" there were no stenosis in Fontaine stage II, and 4 in Fontaine stage III. Out of thet not exceeded 3, 50%, and 1 was subtotal. Likewise, difference can be found of the presence of placks partly in the two groups, partly in the point of view of the stages of Fontaine. There are in group "A" 23 cases with 48 placks, in group "B" 14 cases with 23 placks. Among the patients of group "A" in 10 cases with were in Fontaine II, and 13 in Fontaine III stage. In group "B" 5 were in Fontaine II, and 9 in Fontaine III stage. Authors are calling the attention, that according to their own data, and the sensitivity of duplex scanning this is the most proper examination for recognising the carotid artery sclerosis which is associated with lower limb artery disease.


[The use of multivariate mathematical methods in medical diagnostic systems--a model for the evaluation of cytological smears]. The methods of the multivariate mathematics have been applied in several studies to increase the diagnostic reliability of medical decision support system. In the recent years some new algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both specified by nonlinearity, were developed. This paper provides results for the application of this methods in the area of quantitative cytology and the comparison with the traditional classifiers. 21 normal, 15 dysplastic, 23 malignant, Feulgen stained gastric imprint smears were analysed on a Leitz Miamed DNA equipment. The determination of mean DNA content, the 2c deviation index (2cDI), 5c Exceeding rate (RcER), G1,S,G2 phase fraction ratios, cell nucleus area, form factor was performed. The discriminant analysis classified correctly the 95.6% of malignant cases, 86.7% of dysplasias, and 80.7% normal cases. Our diagnostic system using fuzzy logic made the diagnostic borders fine tuneable, and reliable. The back propagation neural net could classify all three diagnostic groups above 95% correctly. The application of nonlinear computational methods made the diagnostic system more reliable. The application of these algorithms are encouraged.


[Family-centered obstetrics].

[Family-centered obstetrics]. Family centralised delivery model program in the Department of Obstetrics of Borsod County Hospital in Miskolc is reviewed. This program has been started since 1986. Significance and positive emotional effects are emphasized. Preparation for the birth, the presence of the husband in the labour ward, the alternative delivery position and the rooming-in system are discussed in detail. The natural birth's behaviour, which is very important in the life of the family, would be realized with this program.


[Medical treatment of arteriosclerosis obliterans]. The author gives an overview on former and recent ways of medical therapy in peripheral arterial occlusive disease. The importance of possible elimination of the risk factors is emphasized. The author summarizes the mechanism and clinical effects of drugs affecting vasodynamic as well as thrombolytic processes. The conclusion of the review indicates that although presently there is no ideal therapy for the disease, yet in a remarkable part of cases a marked clinical improvement and inhibition of the basic pathologic processes can be produced even by the available preventive and therapeutical methods.


[Bilateral exploration in unilateral inguinal hernia (cost-benefit)]. The authors performed simultaneous inguinal exploration of the right side on 100 girls operated on for the left sided inguinal hernia and hernial sac was found in 73 cases on the right asymptomatic side too. Though the simultaneous bilateral exploration has been proposed by several authors in the case of unilateral inguinal hernia of infants and children, the controversy continues among the pediatric surgeons in this respect at present too. The great number of the hernial sac found on the asymptomatic side according to the authors opinion must be enough to be agreeable with the routine bilateral exploration on girls. There has not been found any publication in the Hungarian literature about this topic.


[D-penicillamine: old drug, new indication? D-penicillamine reduced pulmonary hypertension induced by free radicals]. Pulmonary hypertension is one of the major problems in the neonatal period. Free oxygen radicals play important role in the activation of pulmonary vasoconstriction. Since D-penicillamine has proved to be a strong antioxidant in newborns it was of interest to investigate the effect of the drug in the oxygen radical induced pulmonary hypertension. According to our animal experiments D-penicillamine inhibits the xanthine oxidase induced pulmonary hypertension in piglets. The same inhibitory effect was observed in the prostanoid metabolism. Could D-penicillamine be used in the treatment of pulmonary hypertension in the newborn?


[Spontaneous pneumoperitoneum localized in the left posterior pararenal space in acute pancreatitis]. The authors have analysed the 220 native, erect and supine abdominal X-ray views of 65 males and 45 females with the acute pancreatitis. The localized spontaneous pneumoretroperitoneum inside the left posterior pararenal space was observed in 3.8% of patients (4 cases). The extraperitoneal gas paralleled laterally and inferiorly the margins of kidney and medially the lateral margin of the iliopsoas muscle. Superiorly the gas collection overlay the suprarenal area and outlined the medial crus of the diaphragm, occasionally. The plain-film roentgenogram depended on the quantity of the extraperitoneal gas and of the perirenal fat, besides the subdiaphragmatic adhesions. The pathognostic pneumoretroperitoneum evolved within the initial stage of acute pancreatitis. Afterwards the extraperitoneal gas was hidden by the intraluminal gas bubbles and fluid levels of the dilated small and large bowels.


[Increased use of pancreas transplantation in the management of diabetics]. The surgery looking for new ways takes part in the treatment of the type I diabetic patients. The development of pancreatic transplantation in the last decades is discussed. Nowadays the procedure has become accomplished and widely used in the transplantation practice. According to the results of the clinical trials the pancreatic transplantation can normalize the metabolism and improve the quality of life. By improving also the survival of the simultaneously transplanted kidney the procedure has become increasingly indispensable complement of the kidney transplantation in the treatment of type I diabetic patients with end stage kidney disease.


[New trends in the treatment of exocrine pancreas deficiency]. Economic function of the exocrine pancreas is based on non-parallel synthesis, transport and secretion of pancreatic enzymes during basal state and postprandially. Reserve capacity of acinar cells is also augmented by adaptation to the diet as well as by regeneration. In mild pancreatic insufficiency complex dietetic considerations help to maintain the necessary secretory capacity of the pancreas. In severe cases effective substitution therapy is mandatory and increasing lipase survival by dietetic maneuvers, by optimizing trypsin and chymotrypsin levels as well as acid and bile secretion can significantly ameliorate results of replacement therapy of steatorrhea. However, in painful chronic pancreatitis high protease activities seem to be beneficial. Individual replacement therapy with pancreatin preparations adapted to the requirements of the patient has to be chosen in difficult cases.


[Acute childhood hemiplegia ].

[Acute childhood hemiplegia ]. Stroke in children has been considered to be the most important cause of acute infantile hemiplegia. The author studied 32 patients with childhood stroke. Of the patients 20 had ischemic stroke, and 12 had hemorrhagic stroke. There is an increase of ischemic stroke cases without known predisposing factors in spring. The possibility of nasopharyngeal infection of ischemic stroke in childhood is emphasized.


[Significance of phenotypical properties in extra-intestinal E. coli infections]. Virulence factors (serogroup, haemolysis, haemagglutination, antigens K1, K5, colicinogenicity) and their association with diseases of 3334 Escherichia coli strains isolated from different clinical specimens between 1979-1990 were analysed. Strains, that were isolated from cerebrospinal fluid of newborns under one month were characterized by certain serogroups (O7, O18, O45, O78, O83), possession of antigen K1 and production of colicin. On the basis of their LD50 they belonged to the pathogenic group (i.e. < 10 10(6)) significantly more frequently than those isolated from other materials. Strains originating from blood cultures belonged frequently to serogroup O4, O6, O18 and were haemolytic. Their pathogenicity was proved by mouse lung toxicity test. Properties of strains isolated from wound and throat swabs, urinary samples resembled to that of strains originating from blood cultures in many respects, expressing the fact that bacteria settle in different organs before sepsis is developing. Frequent occurrence of strains with antigen K1, haemolysin and haemagglutination positivity in vaginal swabs expose newborns to danger. Knowledge of virulence markers and prevention of infections are associated.


[Usefulness of exercise test in combination with ECG]. The author gives an overview on usefulness of exercise ECG in cardiology. There is a summary of indications and contraindications of the test and of the personal requirements. The exercise ECG do not recommended to screen asymptomatic individuals. The test is very important in the diagnosis and the prognostic evaluation of patients with ischemic heart disease. The exercise ECG and coronary arteriography are equally important prognostic determinants of future cardiac events. The exercise ECG has been proved an objective tool in the evaluation of functional impairment of patients with congenital and acquired heart disease. The author summarizes the work of exercise laboratories in Hungary, points out the necessity of it's technical improvement and suggests to increase their productivity.


[Esophageal dilatation using the Savary-Gilliard sound set]. Authors present a method of esophageal dilatation and report their experiences. The place of esophageal dilatation among other therapeutic approaches of esophageal stricture is discussed. The advantage of Savary-Gilliard bougies and guide wire and its applications are presented. During one and a half year 218 esophageal dilatations were performed at 82 patients. 11 patients were intubated endoscopically. Esophageal perforation occurred in 2 cases (0.93%). Dilatation of the esophagus with Savary-Gilliard bougies and using of the guide wire are considered a safe and many-sided method in the diagnosis and treatment of esophageal strictures.


[Otoacoustic emission audiometry in neonates and adults]. The authors discuss the clinical use of the otoacoustic emission audiometry. During the physiological process of sound amplification in the cochlea vibration energy escapes from the inner ear. By the analysis of this sound it is possible to gain information about the function of the cochlea. According to the experiences of the authors the method is extremely useful for screening audiometry in pathological and normal neonates. In adults it can be used for monitoring the cochlear function during ototoxic therapy or noise exposure.


[Osteoblastoma in the iliac crest].

[Osteoblastoma in the iliac crest]. An 18 year old male patient is reported with a five year history of mild pain in his right hip. Radiological investigation showed a typical feature for osteoblastoma of iliac bone, with two niduses. En bloc excision was performed. The histological examination's result was also osteoblastoma.


[Experience with surgical treatment of ascendant varicophlebitis]. In ascendant varicophlebitis, the authors suggest not only crossectomy, but also radical removal of the dilated part of the great saphenous vein and of all thrombosed and non-thrombosed varicose veins in one session. They consider it important to clear the extension of the thrombosis by using an ultrasonic doppler flowmeter or the duplex scan technique; phlebography is needed only if deep venous affection is suspected. Cardinal questions of the operative technique are discussed. In cases of deep venous affection, thrombectomy is performed with Fogarty catheter. Antibiotics are generally held to be unnecessary, but early mobilisation and postoperative low-dose heparin prophylaxis are of great importance. No significant complications were detected after 37 interventions. Every patient was controlled one year after surgery. Residual complaints were found more rarely in the radically treated group. As concerns the quick and definitive recovery, mention is made of favourable economic consequences of the active surgical treatment.


[Pseudoaneurysm in a pancreatic pseudocyst]. Four cases with pseudoaneurysm developed on the basis of pancreatic pseudocyst are reported. Regarding data obtained from literature diagnostic and therapeutic possibilities and their success rates are analysed. Authors summarize both specific and non-specific signs of the pancreatic pseudoaneurysm obtained from duplex scan. All of their patients were successfully treated by operation. They call attention to the benefit of the selective feeding artery ligature. Importance of ultrasound follow up of patients suffering from pancreatitis is pointed out, as a prevention of the massive hemorrhage which is the most serious complication of the pancreatic pseudoaneurysm.


[Mortality among mature neonates requiring intensive care]. Causes of mortality among term infants hospitalized in a Neonatal Intensive Care Unit during a period of five years were investigated. Among the 107 fatal cases analyzed, congenital malformation was the cause of death in 63 and hypoxia/asphyxia in 35 cases, whereas 9 newborns died primarily of infection. Though congenital malformation is the leading cause of mortality, nevertheless, also perinatal asphyxia and primary and secondary infections play an important role. The utmost importance of prevention and proper medical care is emphasized.


Identification of complex formation between two intracellular tyrosine kinase substrates: human c-Rel and the p105 precursor of p50 NF-kappa B. Immune complexes of the product of the c-rel protooncogene and of p105, the p50 NF-kappa B precursor, isolated from human T-lymphoblastoid cell lines are comprised of multiple proteins. Only p105 and human c-Rel (hc-Rel) are common to complexes precipitated with antiserum directed against either p105 or hc-Rel. Both proteins are inducible by phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) and their subcellular distribution is affected by this induction. We demonstrate that the Rel immune complex contains a protein with a molecular weight in the 40 kDa range (p40) which apparently is exclusively cytoplasmic. We were not able to detect p40 in the p105 immune complex, though hc-Rel is present. This indicates that hc-Rel exists in different multi-protein complexes and fits a model of functional regulation mediated by differential protein-protein interaction. We also demonstrate considerable isoform diversity of both hc-Rel and p105. We show that this heterogeneity is, in part, the result of phosphorylation. Furthermore, we demonstrate that p105 and hc-Rel are tyrosine kinase substrates. This finding indicates a role for both proteins in intracellular signal transduction pathways which are modulated by modification of their phosphorylation status.


Multiple intragenic elements regulate the expression of the murine N-ras gene. We have identified two separate regions within the murine N-ras transcription unit which may participate in the regulation of N-ras gene expression. One of these regions, localized to the first half of intron 1, contains a site of premature transcriptional arrest. We propose that premature transcription termination, which has been identified as an important control mechanism for several genes, may also play a role in the regulation of the N-ras gene. In addition, we have identified a positively acting region within the N-ras transcription unit. This region, localized to the end of intron 1/beginning of exon 1, was found to greatly increase expression from the N-ras promoter.


Catalytic properties, tissue and intracellular distribution of neurofibromin. The neurofibromatosis type 1 (NF1) gene encodes a protein, neurofibromin, that shows homology with members of the GTPase-activating protein (GAP) family. To study neurofibromin, rabbit polyclonal antisera were raised against two synthetic peptides. These antisera immunoprecipitated a specific protein of about 240 kDa in lysates of adult murine and rat tissues both in the soluble (S100) and to a lesser degree in the particulate (P100) fractions. The neurofibromin immunoprecipitated from the lysates of several murine organs stimulated the intrinsic GTPase activity of p21 c-Ha-ras protein. Based on immunoblotting, immunoprecipitation and GTPase assays, neurofibromin appears to be at least 10-fold more abundant in the brain than in the other murine organs. The GTPase-stimulatory activity of full-length neurofibromin, like the catalytic GAP-related domain, is inhibited by arachidonic acid and the detergent dodecyl maltoside, while phosphatidic acid, containing arachidonic and stearic acid, is non-inhibitory. Immunofluorescence analysis with anti-neurofibromin sera in NIH3T3 cells suggests that at least some of the cellular protein associates with cytoplasmic structures that are distinct from actin or tubulin filaments.


p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas. The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed.


Identification of the product of two oncogenic rearranged forms of the RET proto-oncogene in papillary thyroid carcinomas. In papillary thyroid carcinomas, we have identified two tumor-specific rearrangements of the RET proto-oncogene leading to the formation of different transforming fusion products sharing the tyrosine kinase (tk) domain of the proto-oncogene and designated ptc-1 and ptc-2. We have analysed ptc-1 and ptc-2 products by immunoprecipitation with specific anti-RET antibodies followed by immunoblotting with the same reagent or with antibodies specific for phosphotyrosine (P-tyr) residues. The anti-RET antibodies were reactive with 64-kDa (p64ptc-1) and 81-kDa (p81ptc-2) proteins from lysates of ptc-1 and ptc-2 transformed cells, respectively, and identified two proteins of 140 kDa and 160 kDa from extracts of SK-N-SH, a neuroblastoma cell line previously shown to express two differently glycosylated forms of the normal RET product. The anti P-tyr antibodies, while detecting the same p64ptc-1 and p81ptc-2 proteins from ptc-1 and ptc-2 extracts, did not show any specific band in the neuroblastoma lysates. An additional set of experiments led us to conclude that, whereas the normal product of the RET proto-oncogene is a membrane-associated receptor-like molecule not intrinsically phosphorylated on tyrosine, both oncogenic forms of RET, ptc-1 and ptc-2, are constitutively phosphorylated on tyrosine, display an 'in vitro' autophosphorylation activity, are translocated from the membrane to the cytoplasm and are apparently unaffected by protein kinase C modulation.


Both myeloproliferative disease and leukemia are induced by transplantation of bone marrow cells expressing v-myc. An in vivo system has been established to investigate v-myc-induced hematopoietic neoplasia in mice. A Moloney murine leukemia virus (Mo-MLV)-derived recombinant retrovirus containing v-myc was used to infect immature bone marrow cells, and these cells were then transplanted into lethally irradiated recipients. All provirus-positive reconstituted mice were found to develop hematopoietic proliferative disorders and, in certain cases, overt leukemia--myeloblastic, myelomonocytic and T lymphocytic. In all cases expression of v-myc was high and the disease type did not correlate with the level of expression. We have isolated immortalized monocytes, myeloid progenitors and T lymphocytes from several of these mice and shown tumorigenicity in secondary syngeneic recipients. This system provides a model for investigating the progression from a pre-leukemic disease to malignancy. In addition, we describe a recombinant v-myc-containing retrovirus that directs high-level v-myc expression from the Mo-MLV promoter in all the hematopoietic cell types examined.


PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family. We have isolated two murine cDNAs designated PCTAIRE-1 and -3 which encode putative serine/threonine-specific protein kinases. The predicted products of PCTAIRE-1 and -3 are 65% homologous and are organized into a core 295-residue kinase domain flanked by unique 161 and 117 amino acid N-terminal and 40 and 39 amino acid C-terminal domains respectively. The kinase domains are approximately 50-55% homologous to members of the cdc2/CDC28 kinase gene family, and each contains a cysteine-for-serine substitution within the conserved PSTAIRE motif. PCTAIRE-1 was ubiquitously expressed as a predominant 3.0-kb transcript and a minor 2.2-kb mRNA resulting from differential polyadenylation. In contrast, PCTAIRE-3 exhibited a more restricted pattern of expression with a single 3.0-kb mRNA detected in brain, kidney and intestine. The PCTAIRE-1 and -3 products produced by in vitro transcription-translation failed to bind to p13suc1 but were precipitated by antibodies directed to Schizosaccharomyces pombe p34cdc2 or to the human PSTAIRE motif. Thus, PCTAIRE-1 and -3 are members of a novel subfamily of cdc2/CDC28-related protein kinases.


Activation of the c-Raf protein kinase by protein kinase C phosphorylation. The product of the c-raf-1 proto-oncogene is a cytoplasmic serine/threonine protein kinase that appears to be activated in signal transduction from a variety of cell-surface receptors. The mechanism of c-Raf activation upon stimulation of cell-surface receptors is not clear, but there seem to exist multiple pathways of activation which involve tyrosine and/or serine phosphorylation of the c-Raf protein in vivo. The activated state of Raf is reflected in an increased apparent molecular weight of the Raf protein in sodium dodecyl sulfate-polyacrylamide gels owing to hyperphosphorylation. The tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) is one of the agents able to induce this hyperphosphorylation of Raf in vivo, suggesting that protein kinase C (PKC) may be involved in the activation of c-Raf in particular situations. Using recombinant baculoviruses expressing PKC and Raf polypeptides, we show here that conventional PKC types (alpha, beta, gamma) but not novel types (delta, zeta, eta) or the unrelated Mos kinase are able to activate c-Raf in a TPA-dependent manner upon coexpression in insect cells. Direct phosphorylation of the Raf protein with PKC in vitro also enhanced the kinase activity of c-Raf, suggesting that c-Raf acts immediately downstream of PKC in a protein kinase cascade which is triggered by TPA and may lead to transcriptional activation of TPA-inducible genes and tumor promotion.


AP-1 (Fos-Jun) regulation by IP-1: effect of signal transduction pathways and cell growth. Transcription factor AP-1 is constituted by the various products of the fos and jun proto-oncogene family members, which associate as dimers to bind with variable efficiency to 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive promoter elements (TREs). We have recently shown that DNA binding of AP-1 is regulated by an inhibitory protein, IP-1, whose activity is modulated by phosphorylation. Here it is shown that although AP-1 has a very high affinity for its recognition sequence, its binding to the TRE can be quickly inhibited by the addition of IP-1. IP-1 is more active on AP-1 complexes formed during a shorter period of time. IP-1 activity is blocked by stimulation of the protein kinase C (PKC) signal transduction pathway, achieved by treating HeLa cells with phorbol esters or with a diacylglycerol analog. We observed an increase in AP-1-DNA binding after treatment of the cells with either the calcium ionophore A-23187 or dibutyryl cAMP; this could be ascribed to inhibition of IP-1 activity. A decreased IP-1 activity also correlates with the increase in AP-1-DNA binding after stimulating cells with serum. This suggests that IP-1 is an important target of the various signal transduction pathways. No effect on AP-1 and IP-1 was detected in cells transformed by Ki-ras or v-raf; nor could an effect of inhibition of protein synthesis be observed. We also analysed IP-1 regulation upon differentiation of P19 embryonal carcinoma cells by retinoic acid. We conclude that IP-1 regulation has a pivotal role in the final modulation of Fos-Jun by signal transduction pathways.


Differential induction of c-fos and c-jun proto-oncogenes and AP-1 activity by tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in cells at different stages of tumor promotion in vitro. A two-stage (initiation and promotion) model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the molecular mechanisms of tumor promotion in vitro. C3H10T1/2 cells which had been initiated with a subcarcinogenic dose (0.5 micrograms ml-1) of benzo[a]pyrene (B[a]P) were isolated after 12-O-tetradecanoyl phorbol 13-acetate (TPA) treatment lasting 12, 24 or 36 days. These series of partially promoted cells were designated T-12, T-24 and T-36 cells. T-12 and T-24 cells exhibited higher anchorage-independent growth on soft agar in the presence of TPA than did the initiated or T-36 cells. Cytosolic protein kinase C (PKC) in the resting state was slightly depleted in T-24 and T-36 cells. Proteolytic down-regulation of membrane-bound PKC was enhanced in T-12 cells compared with the initiated cells after 3 h of TPA treatment. Induction of c-fos and c-jun proto-oncogene expression increased two- to threefold in T-12 cells. Moreover, the basal level of c-fos mRNA progressively increased in T-12, T-24 and T-36 cells. As compared with other cell types, T-12 cells had the highest AP-1 DNA-binding activity at both the basal level and at 30 min after TPA treatment. These results indicate that deregulation of the TPA-induced cellular responses occurs in the cells at various stages of tumor promotion, and might be associated with transforming processes.


Identification and quantification of a carcinogen-induced molecular initiation event in cell transformation. All transformed foci of Balb/c 3T3 clone A31-1-1 cells induced by 7,12-dimethylbenz[a]anthracene (DMBA) (42 out of 42 examined) contained an A to T transversion at codon 61 (A182 to T) of the Ki-ras gene. The transformants induced by other carcinogens tested did not contain such a mutation, except one out of nine 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced transformed foci. Thus, we hypothesized that this mutation is a specific DMBA-induced initiating event in Balb/c 3T3 cell transformation and we have measured its frequency of induction before transformation occurs, employing our recently developed method. Such mutations can be detected in the cell population as early as 3 days after exposure to DMBA. The same mutation was also detected in the Ha-ras gene. No detectable level (< 10(-6) of these mutations was induced by other carcinogens tested. The mutation frequency of the Ha-ras gene reached a plateau after 1 week's exposure, but that of the Ki-ras gene continued to increase. These results suggest that the A182 to T mutation of the Ki-ras gene, but not that of the Ha-ras gene, contributes to morphological transformation of Balb/c 3T3 cells. We have demonstrated that the level of expression of ras genes determines the rate of recruitment of cells into transformation. Quantitative analysis of the frequencies of ras gene mutations (initiation) and of transformation suggests that about 25% of those cells with the Ki-ras mutation were recruited into the full transformation process and that, in the presence of the tumor promoter TPA, about 56% of them completed morphological cell transformation.


Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. Fibroblast growth factor receptor (FGFR-1) is expressed as a single 3.5-kb mRNA transcript in normal human melanocytes and in malignant melanomas as determined upon Northern hybridization to a cDNA clone encoding the membrane-spanning form of the human FGFR-1. Polyclonal antisera directed against the chicken FGFR recognized a 145-kDa protein in primary and metastatic melanomas. Antisense oligodeoxynucleotides targeted against the translation start site and a splice donor-acceptor site of human FGFR-1, in addition to inhibiting the proliferation of normal human melanocytes and malignant melanomas, caused extensive dendrite formation and severe disruption of cell-cell contact--morphological changes that were not observed upon inhibition of the genes encoding basic fibroblast growth factor (bFGF) and retinoic acid-alpha receptor. Thus, unlike in the case of the ligand bFGF, expression of the FGFR-1 may represent a requisite to prevent human melanocytes and malignant melanomas from undergoing (terminal) differentiation.


Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype. Human melanoma provides a model to study malignant transformation and tumor progression. Expression of ras oncogenes in cultured normal human diploid melanocytes has induced a subset of phenotypic traits that are characteristic of malignant melanoma cells, including altered morphology, anchorage independence, induction of class II MHC antigens, up-regulation of the ganglioside GD3, and chromosomal abnormalities. However, other characteristics of melanoma, such as loss of expression of adenosine deaminase-binding protein and tumorigenicity, were not observed. We report here that melanocytes infected with a retrovirus containing the viral Ha-ras oncogene underwent complete transformation, acquiring all phenotypic characteristics of malignant melanomas observed in vivo. Transformation occurred in a sequential manner and was associated with spontaneous chromosomal instability. Cytogenetic analysis of transformed melanocytes indicated that the earliest structural chromosomal abnormalities were isochromosomes 6p and 9q followed by complete loss of chromosome 1p, all common karyotypic abnormalities described in human melanomas. The findings suggest that these chromosome regions which are deleted or relatively deficient may contain genes that are critical for the initiation and progression of the melanoma phenotype.


Bone marrow-transforming activity of linker insertion mutants of Abelson murine leukemia virus. Two sets of mutants of the Abelson murine leukemia virus, generated by linker insertion mutagenesis of a cloned proviral DNA, were tested for their ability to transform bone marrow cultures in vitro. All the viruses retained an intact tyrosine kinase domain and were competent for transformation of NIH3T3 fibroblasts in culture. One series contained 12-bp linker insertions in the regions flanking the kinase domain, and the other contained frameshift mutations that truncated the gene product downstream of the kinase domain. The majority of the 12-bp insertion mutants retained full bone marrow-transforming activity; only one insertion in the SH2 domain showed reduced activity. This mutant suggests that some aspect of the SH2 domain may be more important in transformation of lymphocytes than fibroblasts. In contrast to the first set of mutants, the bone marrow-transforming activity of the majority of the truncation mutants was significantly reduced or completely lost. We conclude that there is a broad requirement for an intact C-terminal domain of the v-abl protein for the transformation of pre-B cells, but that no single part of this domain is critical.


The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain. We recently provided evidence that the human tpr gene encodes a 726 amino acid protein (designated tpr-S) and identified an alternatively spliced transcript that encodes a larger tpr protein with an extended C-terminal domain. In this study, through isolation and sequencing of tpr cDNA clones, we have established that this alternatively spliced transcript encodes a protein of 2094 amino acids (designated tpr-L). The larger tpr protein is predicted to have extensive regions of alpha-helix and several stretches of a heptad repeat that is characteristic of proteins adopting a coiled-coil conformation. Furthermore the carboxy domain of this protein is very rich in acidic residues and exhibits homology (58-80%) to the acidic regions of several nuclear proteins, including the Drosophila engrailed protein, Escherichia coli RNA polymerase sigma subunit and nucleolin. To gain additional insight into the function of tpr we examined the expression of tpr transcripts in tissues from adult rat. The highest levels of tpr transcripts were observed in testis, lung, thymus and spleen.


elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding. The ets oncogene superfamily consists of a family of sequence-specific DNA-binding transcriptional activator proteins. We have previously identified, cloned and characterized one of the divergent ets-related members elk-1 and shown that it codes for a sequence-specific DNA-binding transcriptional activator. We have also shown that elk-1 forms SRF (Serum Response Factor) dependent ternary complex with SRE (Serum Response Element), similar to p62TCF. In this report, we have mapped the DNA-binding domain of the elk-1 protein (EDB, elk-1 DNA Binding domain) to the 76 amino acid ets homology region. We have also mapped the SRF interaction domain of the elk-1 protein (ESI, elk-1 SRF Interaction domain) to the carboxy-terminal region of the EDB domain. Ternary complex formation by elk-1 requires both EDB and ESI domains of the elk-1 protein. Our results also show that the EDB domain of the elk-1 protein (residues 1-89) binds SRE autonomously, unlike full-length elk-1 protein, suggesting the presence of a potential Negative Regulatory DNA binding domain (NRD) which prevents the binding of elk-1 protein to SRE. Interaction of SRF with the ESI domain allows the elk-1 protein to bind to SRE. Thus elk-1 belongs to a class of transcriptional factors that are involved in gene regulation not only by autonomous DNA binding but also by indirect DNA binding through recruitment by cellular factors.


c-fos mRNA constitutive expression by mature human megakaryocytes. By in situ hybridization with a c-fos probe, we have shown that human bone marrow megakaryocytes cultured in the presence of 20% aplastic anemia plasma constitutively express c-fos mRNA. At day 0, megakaryocytes are mostly immature and only 3% of them are labeled. The number of labeled cells reached 23% after 12 days of culture. Interleukin 3 (IL-3) and IL-6 added together at day 10 further increased this number to 31% 2 days later. Mature labeled megakaryocytes were more numerous and more strongly labeled than immature ones. These results suggest that c-fos could play a role in megakaryocytic terminal differentiation, either in the polyploidization or in the thrombopoietic function unique to these cells.


Structural organization of a src gene from Xenopus laevis. By sequence analysis of genomic clones, the exon-intron structure of one of the two src genes from Xenopus laevis has been determined. The coding region of the gene is interrupted by 10 introns whose locations are identical to the introns in the coding regions of the src genes of human and chicken. The 5' untranslated region is contained on a separate exon with no sequence conservation relative to the corresponding region of the chicken gene. The 5' untranslated region of the Xenopus gene contains a G + C-rich stem-loop sequence and two ATG triplets. A 1.4-kb fragment containing the 5' untranslated region and sequences upstream of it acts as a promoter when introduced in the correct orientation into X. laevis cell lines. The DNA sequence of this fragment lacks the typical arrangement of TATA and CCAAT sequences but contains the ATGCAAAT octamer sequence and a (TA)39 sequence.


In situ dephosphorylation of p53 protein by calf intestinal alkaline phosphatase treatment. The monoclonal antibody (mAb) 1801 has been reported to identify an N-terminal determinant within the tumor-suppressor protein p53 located between amino acids 32 and 79. This region contains two potential sites for serine phosphorylation at amino acids 33 and 46. Using a novel technique which dephosphorylates proteins in situ in fixed permeabilized cells, we have unmasked determinants in p53 recognized by mAb 1801, allowing additional sites of p53 protein to be detected in immunohistochemically reacted cells. This result indicates that phosphorylation at one or both sites within the determinant recognized by mAb 1801 previously blocked antibody-ligand interaction. It further suggests that in situ dephosphorylation may be of more general use in identifying antibodies which can only bind to epitopes in a particular phosphorylation state.


A possible role for c-Myc oncoproteins in post-transcriptional regulation of ribosomal RNA. Overexpression of members of the myc family of oncogenes contributes to the development of many vertebrate malignancies. Although several functions for myc gene products have been proposed, the targets for Myc activity during oncogenesis or normal development remain to be identified. Oocytes of Xenopus laevis, which are non-dividing cells that accumulate abundant c-Myc protein, provide an unusual opportunity to examine c-Myc function. We have investigated whether the accumulation of massive amounts of ribosomal RNA (rRNA) by Xenopus laevis oocytes may be related to their elevated expression of myc proto-oncogenes. Our data show that anti-Myc antibodies and some (but not all) c-Myc peptides from conserved regions of the c-Myc protein enhance the turnover of rRNA synthesized in homogenates of oocyte nuclei. These results suggest that one or more members of the Myc protein family may be involved in post-transcriptional regulation of rRNA metabolism. The regulation by c-Myc of rRNA could account, in part, for the generalized stimulation of cells during tumorigenesis.


[Otorhinolaryngologic problems of Wegener's granulomatosis of three months duration]. A case of Wegener's granulomatosis in a 30 years old female was described. The authors have presented the diagnostic difficulties and treatment this rare disease.


[Reinke's edema].

[Reinke's edema]. The authors present a theoretical discussion about the histological and anatomical structure of Reinke's space as well as the etiology, clinical features and treatment of Reinke's edema.


[Complex method of treating chronic, irreversible peripheral facial palsy particularly considering rehabilitation postoperatively]. Authors described the scheme of the functional reconstruction of the face in patients with protracted, irreversible, peripheral facial palsy and the subsequent rehabilitation. A new, own method of treatment has been introduced considering anatomical and functional relations.


[Ultrasonic examination of the larynx].

[Ultrasonic examination of the larynx]. The aim of our work was the application of sonographic method of the larynx. Aloka Hellige type SSD 280 'LS was used on the examination in real time. Sonographic images of the larynx were obtained in 25 healthy human and 25 healthy children. Sonography may probe to be a potentially useful technique for the examination of the larynx.


[Evaluation of surgical techniques used in treating microtia for 35 years]. The author presents an evaluation of the results of surgical treatment in 346 patients with microtia, treated in the previous 35 years, by using different materials to reconstruct the auricle. The reasons for giving-up the application of xenogenic and allogenic cartilage as well as polyester-polypropylene implants to reconstruct the auricular skeleton are explained. A 17-year experience of using autogenic costal-cartilage to reconstruct the auricular skeleton helps to state that early and late complications have been reduced and satisfactory esthetic results have been obtained. To meet their need, the patients were treated for the associated malformations by means of plastic and reconstructive procedures and were referred to other specialists--orthodontic, otologic and prosthetic.


[Metastatic tumors of the orbit].

[Metastatic tumors of the orbit]. The authors described patients with metastatic tumors, treatment in 1985-1990 year in Otolaryngologist Department Medical Academy in Kraków and dealing with the diagnosis and treatment. It is usually easy treatment the patients with orbital tumors but is very difficult when the orbital tumors are metastatic neoplasms of the orbita.


[Stellectomy in the treatment of patients with long QT syndrome]. The authors present the surgical technique of stellate ganglion excision as a therapeutic method in patients with the long QT syndrome. The operations were performed through an anterior supraclavicular approach. Discussing the anatomic considerations, the possibilities of complications and side effects, both temporary and permanent, including Horner's syndrome are reviewed. On the base of the review of present literature and the postoperative results in patients treated in the Otolaryngological Department of the Medical Academy in Bydgoszcz, the authors confirm that the results of stellate ganglion excision in patients with the long QT syndrome are encouraging, but the possibilities of complications, including sudden death after stellectomy, must be taken into consideration.


[Retrospective analysis of mortality due to neoplasms of the larynx in Jelenia Góra district (1982-1989)]. The authors presents a retrospective analysis of mortality from laryngeal cancer in the population of Jelenia Góra in the years 1982-1989. The analysis was based on the death register books and cards.


[Fine needle aspiration biopsy in the diagnosis of head and neck tumors]. The results of 3039 fine needle aspiration biopsies of the head and neck tumors were presented. The comparison of cytological and histological examinations in 1141 patients showed that correct cytological diagnosis was established in 84.2% of cases.


[Determination of oxidative activity of ceruloplasmin using Ravin's method in patients with laryngeal carcinoma]. According to Ravin's method an oxidative activity of ceruloplasmin was determined in the group of patients with carcinoma of the larynx before and after a surgical treatment, in the group of patients with inflammatory lesions in the upper respiratory tract and in the control group of healthy individuals. As a result of this assay the significantly increased of oxidative activity ceruloplasmin was obtained in the individuals with the carcinoma of the larynx (before surgical treatment) in comparison to the group of patients suffering due to inflammatory diseases of the upper respiratory tract and to the group of healthy subjects. Simultaneously a significant decrease of the oxidative activity of serum ceruloplasmin in the individuals with carcinoma of the larynx after a previous surgical treatment was observed.


[Evaluation of the ear and vestibular apparatus depending on the anatomy of the cervical spine]. Function of the acoustic organ and the vestibular organ in correlation from radiograph of cervical spinal column was examined in 102 patients aged 20-68 years, of both sexes. The obtained results of audiometric and electronystagmographic investigations have shown that the greatest disorders of function of the acoustic organ and the vestibular organ was at the patients with osteophytes and discopathy in cervical spinal column. Impaired hearing and vestibular disorders was observed also at the patients with normal radiograph of cervical spinal column. The authors have thought that the above deviations can be caused by irritation even the discreet degeneration of cervical spinal column, which ones conduct to increased tension of sympathetic system.


Komputerwa analiza, identyfikacja i graficzna prezentacja badań ABR--system audiometrii klinicznej. [Computer analysis, identification and graphic representation of ABR research--clinical audiometric system]. A microcomputer-based system for auditory evoked potentials and tonal audiometry. The software which directs stimulus generation, data recording, displaying and analysis is written in Pascal 5.5. The system hardware is commercially available and of own components.


Wplyw rodzaju bodzća dzẃiekowego na oznaczanie progu slichowego metoda ABR. [The effect of brief tone envelopes on ABR and behavioral thresholds]. The present study examines the effect of brief tone envelopes on ABR and behavioral thresholds in small groups of normal and hearing-impaired subjects. The hearing-impaired subjects had very steep high-frequency hearing loss in 2-6 kHz region. The stimuli for both ABR and behavioural estimates were 2 and 4 kHz tone burst with linear and nonlinear envelopes. Behavioural thresholds were estimated using a computer controlled, modified block up-down method. The ABR thresholds were evaluated from the recordings collected in automatic acquisition process. Results of our experiments showed that for different stimulus envelopes both behavioural and ABR thresholds were similar in normal range of hearing. However, for impaired ears at high frequencies, both psychoacoustic and ABR thresholds differ, sometimes quite significantly, depending on stimulus envelope.


Badania wywolanej otoemisji akustycznej. [Tuning properties of the evoked otoacoustic emission]. The authors present the investigation of evoked otoacoustic emission (EOAE) as a part of the studies of the inner ear function. The EOAE was obtained in 10 normal hearing subjects during the routine recording conditions. In the investigation was used the adjustment of masking tone to obtain a reduction in the (EOAE) most stable component amplitude and suppression of the (EOAE) frequency components (FFT--derived).


[Mucociliary transport in the upper airways]. The current views of the ciliary function of the respiratory epithelium are presented. Mucociliary transport in the nose, maxillary atrium, frontal sinus, middle ear and the eustachian tube are discussed.


Kanamycin inhibits cochlear-renal ODC in neonatal rats. Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is important in development and regeneration. We hypothesize that aminoglycoside inhibition of ODC mediates developmental hypersensitivity to aminoglycoside ototoxicity. Kanamycin effects on ODC activity (decarboxylation of ornithine) in vitro were determined in the postmitochondrial fraction of cochlear and renal homogenates from 11-day-old rats. Kanamycin inhibited cochlear and renal ODC by an uncompetitive mechanism. For the cochlear enzyme, the inhibitor constant (Ki) for kanamycin was 99 +/- 25 mumol/L; for the renal enzyme, the Ki = 1.5 +/- 0.1 mmol/L. In vivo effects of kanamycin on cochlear, renal, brain ODC activity were determined in rats treated with kanamycin (400 mg/kg/day, intramuscularly) or saline during postnatal days 11 through 20, the hypersensitive period for ototoxicity. Rats were killed on postnatal days 12, 14, 16, and 20 and ODC was assayed. Kanamycin significantly inhibited ODC in the lateral wall-organ of Corti and kidney (ANOVA alpha = 0.05), but had no effect on cochlear nerve and no consistent inhibitory effect in the brain. These results suggest that ODC is a potential target of kanamycin in susceptible tissues and may be a contributing factor in developmental sensitivity to the drug by inhibiting repair and developmental processes mediated by ODC.


Pseudomonas otitis media after eustachian tube obstruction. Previous experiments have shown that Pseudomonas aeruginosa may infect the middle ears of chinchillas by way of the eustachian tube and that chinchillas with acute otitis media (AOM) are more susceptible to pseudomonas infection than animals without AOM. The purpose of this experiment was to examine the effects of otitis media with effusion (OME), induced by means of eustachian tube obstruction, on middle ear susceptibility to nasal inoculation of P. aeruginosa. Chinchilla eustachian tubes were obstructed with silicone rubber sponge bilaterally; OME developed in eight animals (11 ears)--three bilaterally and five unilaterally--and persisted for 6 months. Ten chinchillas with normal eustachian tube function served as controls. All animals were nasally inoculated with 5 x 10(6) colony-forming units of P. aeruginosa. Pseudomonas otitis media developed in eight of 11 OME ears with effusion, none of five ears without OME, and four of 20 control ears (chi 2 = 11.782, p = 0.003). Therefore, P. aeruginosa can infect the middle ear by way of the eustachian tube. Tubal dysfunction may lead to the development of chronic suppurative otitis media by increasing tubotympanic susceptibility to opportunistic pathogens.


Effect of asymmetric vocal fold stiffness on traveling wave velocity in the canine larynx. The vocal fold (VF) traveling wave is essential to normal voice production. The present investigation describes a new method to determine traveling wave velocity (TWV) in the in vivo canine phonatory model. This method synchronizes photoglottographic and electroglottographic waveforms with videostroboscopic images to determine the duration of time the traveling wave moves between two tattoos placed a known distance apart between the upper and lower margins of each VF. Using this method, we compared the TWV of a paralyzed VF with the TWV of the contralateral, electrically stimulated VF during phonation in two canines. In addition, the presumed VF stiffness asymmetry in the simulated acute recurrent laryngeal nerve paralysis state was confirmed by measuring Young's modulus of each VF. The results indicated that the TWV of the paralyzed VF averaged 55% of the TWV of the normal, stiffer VF when the glottal gap was small and entrainment occurred. This study demonstrated the feasibility of quantifying traveling wave motion in asymmetric VF stiffness disorders. The potential use of TWV in human beings as a target to optimize the phonosurgical results in asymmetric VF stiffness disorders is discussed.


Is human galvanically induced triceps surae electromyogram a vestibulospinal reflex response? Interest in understanding the human vestibulospinal reflex has increased enormously over the past three decades, because this reflex is the primary effector of maintenance of posture and balance. On a posture platform, forces exerted by the triceps surae (TS) and tibialis anterior muscles are measured to calculate center of mass sway. We wished to determine whether the TS response is a direct component of the vestibulospinal reflex. Ten healthy human beings were stimulated with sinusoidal galvanic currents delivered over their mastoid processes. Sway response on a posture platform and TS electromyogram (EMG) were recorded for the following conditions: (1) standing unrestrained; (2) standing completely restrained above the leg; and (3) sitting unrestrained. Results were similar for all subjects. Computer-aided analysis for case 1 reveals that TS EMG and horizontal body sway responses are generated at the same frequency as the stimulating current, with a phase lag of 90 degrees. For case 2, body sway response and any component of the TS EMG over the unstimulated condition were absent in all subjects. For case 3, body sway persisted, but no TS EMG above the unstimulated condition was recorded. As the TS EMG disappears when the standing subject is restrained from swaying or in the unrestrained seated subject, we conclude that the TS EMG response is compensatory to motion of more superior portions of the musculoskeletal system; it is not part of the vestibulospinal reflex.


Early mucosal changes in experimental sinusitis. Normal mucociliary flow is a significant defense mechanism in the prevention of acute sinusitis. We have undertaken a study to examine the early sinus mucosal and mucociliary changes that occur in response to acute infection. Twenty rabbits were evaluated for 5 days after an obstructed maxillary sinus was inoculated with either Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, or a sterile saline solution. Data collected included measurements of sinus mucosal ciliary beat frequency, quantitation of ciliated cell losses, and electron microscopic observations. Results demonstrate statistically significant (p < 0.05) changes in mucosal ciliary beat frequency that were either excitatory or inhibitory, depending both on the length of the infection and the specific organism. No changes in ciliary beat frequency were observed in the control animals (p > 0.55). Control animals likewise demonstrated no loss of ciliated cells from mucosal epithelium; however, dramatic losses of ciliated cells from the sinus mucosa of the experimental groups were observed. These losses occurred at different rates, depending on the infecting organism, but all infected groups demonstrated a > 86% decrease in the number of viable ciliated cells from the sinus mucosa after sinusitis of 5 days duration. We conclude that a significant loss of ciliated cells from sinus mucosa and a corresponding disruption of normal mucociliary flow occurs early after exposure to pathogenic organisms and is a significant predisposing factor in the development of acute sinusitis.