bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylaxis of oral mucositis associated with chemoradiotherapy for oral carcinoma by Azelastine hydrochloride (Azelastine) with other antioxidants
Authors: Osaki Tokio , Ueta Eisaku , Yoneda Kazunori , Hirota Jusui , Yamamoto Tetsuya
Published: February 2007

Background. One of the dose‐limiting adverse effects of chemoradiotherapy is mucositis, especially oral mucositis. Prophylaxis of severe mucosal reaction would allow application of aggressive chemoradiotherapy to malignancies.

Methods. Sixty‐three patients who received inductive concomitant chemoradiotherapy with cobalt 60 (60Co1 ∼ 30 Gy), peplomycin (PLM, ∼ 38 mg), and 5‐fluorouracil (5‐FU, ∼3,500 mg) were included in this study. From the start of therapy to the disappearance of oral erosion, 37 patients received daily doses of Azelastine (2 mg) + vitamin C (500 mg) + vitamin E (200) + glutathione (200 mg) (azelastine group), whereas the other 26 patients received the same regimen without azelastine (control group). The severity of oral mucositis in both groups was evaluated periodically.

Results. At 10 Gy with 15 mg PLM and 1,250 mg 5‐FU, grade 1 mucositis (redness of the oral mucosa) was induced in 14 patients in the control group and five patients in the Azelastine group. At 20 Gy with 30 mg PLM and 2,500 mg 5‐FU, grade 2 (erosion with mild irritation) and grade 3 (extensive erosion with marked irritation) stomatitis were observed in 9 and 3 of the control patients and 5 and 1 in the Azelastine group, respectively. At the completion of treatment, mucositis in 21 patients in the Azelastine group remained at grade 1 or grade 2, whereas grades 3 and 4 (ulceration with severe contact pain) mucositis were observed in 6 and 10 patients, respectively. However, in the control group, grades 1 and 2 were observed in only 2 and 3 cases, whereas grades 3 and 4 stomatitis were induced in 6 and 15, respectively. Azelastine suppressed neutrophil respiratory burst both in vivo and in vitro, and also suppressed cytokine release from lymphocytes. However, neutrophil superoxide dismutase (SOD) activity was negligibly suppressed.

Conclusion. A regimen including Azelastine, which suppresses reactive oxygen production and stabilizes cell membranes, may be useful for the prophylaxis of mucositis due to chemoradiotherapy. © 1994 John Wiley & Sons, Inc.
An unusual case of synchronous thyroid and parathyroid adenomas
Authors: Huston Butch M. , Landas Steve K.
Published: February 2007

A 52‐year‐old woman was evaluated for an enlarging neck mass. Fine‐needle aspirate contained Hürthle cells and thyroidectomy revealed two separate thyroid morphologically similar lesions. Immunohistochemical studies confirmed diagnoses of separate Hürthle cell thyroid and oxyphil parathyroid adenomas. Diagnostic pitfalls and the role of immunohistochemistry in diagnosis are discussed. © 1994 John Wiley & Sons, Inc.
4NQO carcinogenesis: A mouse model of oral cavity squamous cell carcinoma
Authors: Hawkins Brian L. , Heniford Briana W. , Ackermann Douglas M. , Leonberger Michael , Martinez Serge A. , Hendler Fred J.
Published: February 2007

Background. A murine model of oral cavity carcinogenesis is needed to study the molecular aspects of malignant transformation. 4‐Nitroquinoline‐1‐oxide (4NQO), a water‐soluble carcinogen, produces squamous cell carcinoma in rodents. Protocols were designed to investigate the temporal aspects of neoplastic transformation.

Methods. 4NQO was applied topically to mouse palates for up to 16 weeks. Mice were observed and killed from 24 to 49 weeks.

Results. A spectrum of lesions ranging from atypia to moderately differentiated invasive squamous cell carcinoma (SCC) was produced. The severity of the lesions corresponded to the duration of treatment and the length of observation. There was no gross or microscopic evidence of an inflammatory reaction to 4NQO. The lesions were focal and normal mucosa predominated in the treated mice.

Conclusion. 4NQO reliably produced preneoplastic and malignant oral cavity lesions, which morphologically and histologically mimic human head and neck cancer. Lesions develop long after 4NQO exposure and without an inflammatory response. Thus, the model should be useful for molecular analysis of neoplastic transformation. © 1994 John Wiley & Sons, Inc.
Recurrence of laryngeal or hypopharyngeal primary tumor after radical neck dissection for postradiotherapy neck nodal metastases
Authors: Ho Chiu M. , Lam Kam H. , Wei William I. , Lam Lai K. , Yuen Po W.
Published: February 2007

Background. When the primary tumor in the larynx or hypopharynx responds well to radiotherapy, nodal metastasis in the neck may persist or recur. The primary site is usually left alone when no lesion is evident, but its long‐term control is uncertain.

Methods. Radical neck dissection was performed in 23 patients who had nodal metastasis, while the primary tumor in the larynx or hypopharynx was controlled after radiotherapy. The primary site was left alone and kept under surveillance.

Results. Seven patients (30%) had recurrence at the primary site on follow‐up. Two significant risk factors for development of recurrences at the primary site were identified: the neck node staging at presentation (p < 0.03) and presentation with persistent neck lymph nodes (p < 0.03). The 2‐year survival of those patients with recurrences at the primary site was 29%.

Conclusion. Radical neck dissection alone was justified, but close surveillance of the primary site after surgery is mandatory, especially for those patients with high‐risk factors.
Large thyroglossal duct cyst with laryngeal extension
Authors: Shaari Christopher M. , Ho Bryan T. , Som Peter M. , Urken Mark L.
Published: February 2007

Background. A thyroglossal duct cyst typically presents as a long‐standing neck mass that becomes symptomatic when inflamed. Hoarseness is an uncommon complaint, and its association may suggest encroachment on and destruction of the larynx. Following removal of the cyst with the Sistrunk procedure, the larynx may need to be reconstructed.

Methods. A case is reported of a patient who was initially seen with hoarseness and a long‐standing midline neck mass. Computed tomography (CT) demonstrated a large cystic neck mass that eroded the thyroid cartilage and encroached on the pre‐epiglottic space and right paraglottic space. Although the clinical impression was that of laryngeal neoplasm, the CT diagnosis was that of a cyst. At surgery, a thyroglossal duct cyst was found and successfully removed with the Sistrunk procedure. Because the thyrohyoid membrane and thyroid perichondrium were preserved, the glottis did not require reconstruction. This case is presented and the literature of thyroglossal duct cysts that extend into the larynx is reviewed.

Conclusions. The clinical and radiographic criteria that suggest encroachment of a thyroglossal duct cyst on the larynx are reviewed. The management and indications for laryngeal reconstruction are discussed.
Prognostic significance of prostaglandin E2 production in fresh tissues of head and neck cancer patients
Authors: Snyderman Carl H. , Milanovich Michele , Wagner Robin L. , Johnson Jonas T.
Published: February 2007

Background. Immunosuppressive prostaglandins may play a role in the biologic behavior of head and neck cancer. Increased levels of prostaglandin E2 (PGE2) have been measured in squamous cell carcinoma of the head and neck (SCCHN).

Methods. To address this question, tissue levels of PGE2 were measured in tumor tissues, normal mucosa, and lymph nodes of 37 patients undergoing tumor resections. Tissue specimens were placed in culture media, and levels of PGE2 released into the supernatant were measured by radioimmunoassay.

Results. Tissue levels of PGE2 were significantly greater in tumor and normal mucosal tissues compared to lymph nodes (p = 0.0003). There was no difference between metastatic and tumor‐free lymph nodes. Although tumor tissue levels of PGE2 were not associated with tumor stage, increased levels of PGE2 were associated with increased 2‐year disease‐free survival (p = 0.02).

Conclusions. Although PGE2 may have adverse effects on local immune function in tumor tissues, improved survival of patients with increased local PGE2 production may be indicative of an enhanced immunologic response to the tumor which has a favorable impact on outcome. © 1995 Jons Wiley & Sons, Inc.
Supraomohyoid neck dissection as a staging procedure for squamous cell carcinomas of the oral cavity and oropharynx
Authors: Henick David H. , Silver Carl E. , Heller Keith S. , Shaha Ashok R. , El Gady Har , Wolk David P.
Published: February 2007

Background. A multi‐institutional retrospective study was performed to evaluate the efficacy of the supraomohyoid neck dissection (SOHND) for detection of occult cervical metastasis in squamous cell carcinoma of the oral cavity and oropharynx.

Methods. Seventy‐five previously untreated patients with clinically negative necks were studied. Seventeen (23%) neck specimens revealed occult metastatic disease, and 58 (77%) were histologically negative. Postoperative irradiation was received by 94% of the patients with positive specimens and 22% with negative specimens. Patients were followed until recurrence of neck disease, or for a period of 2 years or longer.

Results. Cervical metastasis subsequently developed in 25% of treated positive specimen patients, none of the untreated positive specimen patients, 8% of the treated negative specimen patients, and 11% of the untreated negative specimen patients. The sensitivity of SOHND for cervical metastasis was 82%, negative predictive value 91%, and accuracy 94%.

Conclusions. The authors conclude that SOHND is a useful procedure for detection of occult cervical metastatic disease in cancer of the oral cavity and oropharynx. © 1995 Jons Wiley & Sons, Inc.
Tension pneumocephalus following craniofacial resection
Authors: Wanamaker John R. , Mehle Mark E. , Wood Benjamin G. , Lavertu Pierre
Published: February 2007

Background. The craniofacial approach is a reliable method for excising tumors involving the anterior skull base. Advances in technique have minimized complications. Although cerebrospinal fluid leaks and meningitis are well known complications, tension pneumocephalus is not well described. We review two cases and discuss the pathophysiology, clinical manifestations, radiographic features, and treatment of tension pneumocephalus.

Methods. Case study. We reviewed the records of all patients who underwent anterior craniofacial resection at our institution, a tertiary care center, from 1976 to 1993. Among 45 patients identified, 2 had tension pneumocephalus.

Results. Neurologic deterioration after anterior craniofacial resection occurred in both patients in the immediate postoperative period. Both patients had extradural intracranial air under pressure and were diagnosed with tension pneumocephalus. In one patient, this was treated by needle aspiration followed by catheter drainage, and the second patient was treated with needle aspiration followed by airway diversion. The first patient recovered fully and was discharged on postoperative day 14; the second patient's mental status did not return to the preoperative level, and he was discharged on postoperative day 23 to a rehabilitative facility. Approximately 3 months later, his level of mentation returned to baseline.

Conclusions. Tension pneumocephalus is a potentially devastating complication that may occur after craniofacial resection. It requires prompt recognition and treatment to minimize morbidity. © 1995 Jons Wiley & Sons, Inc.
Mesenteric flap in free jejunal transfers: A versatile technique for head and neck reconstruction
Authors: Yamamoto Yuhei , Nohira Kunihiko , Shintomi Yoshihisa , Yoshida Tetsunori , Minakawa Hidehiko , Okushiba Shunichi , Fukuda Satoshi , Inuyama Yukio , Hosokawa Masao
Published: February 2007

Background. The technique of free jejunal transfers has been widely used for pharyngoesophageal reconstruction. However, secondary infectious and fistulous complications may develop in extensive and preoperatively high‐dose irradiated cases.

Methods. A generous jejunomesenteric composite graft was harvested and the mesenterium was effectively applied for head and neck reconstruction.

Results. The mesenteric flap connected with the revascularized jejunum was used as means for obliterating dead space in the head and neck region, as a cover for the cervical vessels, as a vascularized bolstering for the vascular and enteral anastomoses, or as a vascularized bed for skin grafting when the skin flaps are deficient. Only one small fistula occurred in 10 patients who underwent the mesenteric flap.

Conclusions. This versatile technique is expected to reduce the incidence of postoperative complications in pharyngoesophageal reconstruction using free jejunal transfers. © 1995 Jons Wiley & Sons, Inc.
Combined V figure‐shaped scapular osteocutaneous and latissimus dorsi myocutaneous flap for composite mandibular reconstruction
Authors: Yamamoto Yuhei , Nohira Kunihiko , Yamashita Tetsuro , Shintomi Yoshihisa , Hosokawa Masao , Furukawa Hiroshi , Sugihara Tsuneki , Ohura Takehiko
Published: February 2007

Background. As early as 1981, the scapular crest was reported as a versatile donor site of vascularized bone flap. In our institute, much attention has been paid to applying a compound flap based on the subscapular vascular system for composite mandibular reconstruction.

Methods. The combined V figure‐shaped scapular osteocutaneous and latissimus dorsi myocutaneous flap has been used for primary or secondary reconstruction of the mandible, intraoral mucosa and/or external skin following major ablation of the malignant tumors in seven patients.

Results. There was one total flap failure. Satisfactory results were obtained in the remaining patients.

Conclusions. The V figure‐shaped scapular bone flap supplied by the angular branch provides a long rotation arc of vascular pedicle, a long bony segment of more than 14 cm, and a good contour of mental protuberance. The combination of the scapular osteocutaneous flap with latissimus dorsi myocutaneous flap allows reliable reconstruction of massive and three‐dimensional composite mandibular defects. © 1995 Jons Wiley & Sons, Inc.
Epiglottic abscess
Authors: Stack Brendan C. , Ridley Marion B.
Published: February 2007

Background. Epiglottitis is more commonly seen in children less than 6 years of age, although this entity has also been well described among adults. A coalescence of infection of the epiglottis, or epiglottic abscess, has been infrequently reported in series of epiglottitis. Risk factors for epiglottic abscess include adult age at onset, diabetes, and the presence of a foreign body.

Methods. Case study.

Results. We present a case of a woman with a 4‐day history of febrile illness, odynophagia, and an altered voice. Clinical examination and computed tomography (CT) demonstrated an epiglottic abscess. The patient underwent direct laryngoscopy, intubation, drainage of abscess, and intravenous antibiotics.

Conclusions. The diagnosis of epiglottic abscess should be considered in adult patients initially seen with odynophagia and dysphonia. Principles of treatment include airway management, antibiotics, and surgical drainage. © 1995 Jons Wiley & Sons, Inc.
Anomalies of forearm vascular anatomy encountered during elevation of the radial forearm flap
Authors: Funk Gerry F. , Valentino Joseph , McCulloch Timothy M. , Graham Scott M. , Hoffman Henry T.
Published: February 2007

Background. The radial forearm flap has gained considerable popularity over the past 10 years. With the increasing number of forearm flaps being used in head and neck reconstruction, it is likely that anomalous forearm vascular anatomy will be encountered by more head and neck surgeons performing this procedure.

Methods. We reviewed our experience with 52 forearm flaps; four different anomalies of forearm vascular anatomy were encountered in four patients. In this article we present each of our cases and discuss the incidence, preoperative diagnosis, and recommended management of these and the more common forearm vascular anomalies.

Results. The anomalies encountered in our series include: one case of distal takeoff of the radial artery deep to the pronator teres muscle, two cases of a superficial dorsal antebrachial artery, one case of bilateral hypoplastic ulnar arteries, and one case of high takeoff of the radial artery.

Conclusions. There are a number of anomalies of forearm vascular anatomy of clinical significance to the surgeon performing these procedures. Most of these anomalies can be identified with a careful preoperative examination. Surgeons performing this procedure should be familiar not only with the normal vascular anatomy of the forearm flap, but also with the more common anatomic variants. Failure to recognize or appropriately manage these anomalies of forearm vascular anatomy may result in a compromised surgical outcome. © 1995 Jons Wiley & Sons, Inc.
Hypothyroidism in association with systemic amyloidosis
Authors: Rich Michael W.
Published: February 2007

Background. Systemic amyloidosis leads to functional compromise of various organs through infiltration of these tissues by amyloid protein. The majority of affected patients develop infiltration of the thyroid gland; yet thyroid dysfunction rarely occurs.

Methods and Results. Described herein is a case of hypothyroidism occurring in a patient with amyloid goiter. An alternative explanation for her hypothyroidism could not be determined by histologic or serologic evaluation. Hormonal assays were consistent with progressive hypothyroidism in spite of oral and, finally, parenteral replacement therapy. A review of the literature describes other cases of thyroid dysfunction reported in patients with systemic amyloidosis.

Conclusions. This case illustrates how amyloid infiltration may be a cause of hypothyroidism in patients with systemic amyloidosis. Therefore, all patients who develop a goiter, including those with systemic amyloidosis, must be screened for thyroid dysfunction. When a physician diagnoses the patient with hypothyroidism, that physician must be aware of potential pitfalls in the administration of thyroxine replacement as outlined below.
Intracranial extension of sphenoid sinusitis
Authors: Xenos Chris , Rosenfeld Jeffrey V. , Kleid Stephen M.
Published: February 2007

Background. The incidence of sphenoid sinusitis has decreased significantly since the pre‐antibiotic era. Intracranial complications from isolated sphenoid sinusitis are rare but have a high morbidity and mortality.

Methods. A case of intracranial extension of sphenoid sinusitis in a 64‐year‐old woman is reported.

Results. A 64‐year‐old woman was initially seen unconscious with bacterial meningitis and cerebrospinal fluid (CSF) fistula. Imaging suggested sphenoid sinusitis with intracranial extension. She underwent a sinus drainage procedure, was placed on antibiotic therapy, and underwent a definitive sphenoid sinus obliteration. The patient made a satisfactory recovery.

Conclusions. Despite the low incidence of intracranial complications of sphenoid sinusitis, the potential morbidity and mortality from such complications is high. We advocate aggressive management consisting of antibiotic therapy, sinus drainage, and definitive CSF fistula repair. © 1995 Jons Wiley & Sons, Inc.
Adverse aspects of small thyroid cancer and need for treatment
Authors: Rosen Irving B. , Azadian Abbas , Walfish Paul G.
Published: February 2007

Background. Small, well‐differentiated thyroid cancer (tumor <1.5 cm) is frequently dismissed as biologically inconsequential, although varied reports have offered differing experiences.

Methods. A total of 382 thyroid cancer patients were reviewed. Of these, 99 patients had tumors that were < 1.5 cm. Thirty‐five patients in this group with positive nodes, extrathyroidal invasion, or metastatic disease were studied.

Results. Thirty‐five patients (one‐third of the <1.5 cm group) showed other sites of involvement: nodes, 28; lung, 1; muscle, 7; nerve, 5; and bone, 2. Six patients had residual cancer following surgery. Surgery included thyroidectomy and neck dissection as well as orthopedic procedures for metastatic bone disease. Radioiodine ablation was used in 33 patients, external radiation in 5. Thirty‐one patients are well without disease, 3 are alive with disease, 1 died of disease.

Conclusions. Small, well‐differentiated thyroid cancer is infrequently aggressive, but it may be a source for metastatic morbidity and recurrence and can be viewed as potentially lethal. Need for treatment should not be ignored based solely on the size of the tumor. © 1995 Jons Wiley & Sons, Inc.
Maneuver to assist examination of the hypopharynx
Authors: Purser Simon , Antippa Phillip
Published: February 2007

Background. The lower hypopharynx, lying posterior to the larynx, is not usually assessable during outpatient examination. A maneuver was developed to assist flexible endoscopic examination of this region. The discomfort experienced by fifty consecutive patients undergoing the maneuver was assessed together with the view obtained.

Method. Fifty patients assigned scores from 0 to 10 to the discomfort experienced during manual anterosuperior traction applied to the prelaryngeal skin, together with two other commonly performed procedures. The view obtained in the last 30 patients was assessed.

Results. The mean discomfort score for the maneuver was 3.77, compared with 3.84 and 5.94 for the other two procedures.

A view to the cricoarytenoid joint or below was obtained in 60% of the patients assessed.

Conclusions. We conclude that the maneuver is well tolerated and results in a useful view of the hypopharynx in the majority of patients.

No prior report of this maneuver has been found in the literature.
Mortality in the pediatric patient with tracheotomy
Authors: Dutton Jay M. , Palmer Phyllis M. , McCulloch Timothy M. , Smith Richard J. H.
Published: February 2007

Background. The mortality rate of children with tracheotomies is estimated to be between 11% and 40%, although the incidence of tracheotomy‐related deaths is only between 0% and 3.4%. The purpose of this report was to analyze the mortality rate in children with tracheotomies.

Methods. A review of the medical records of children at the University of Iowa Hospitals and Clinics who underwent tracheotomy over a 15‐year period ending in 1989 was performed. Data were analyzed in 5‐year time blocks (Block 1, 1975 to 1979; Block 2, 1980 to 1984; and Block 3, 1985 to 1989).

Results. Fifty‐two patients died with tracheotomy tubes in place. In 4 patients, the cause of death was tracheotomy related. Three of these patients were under 5 years of age and died secondary to tracheotomy tube displacement or obstruction; one patient, an 18‐year‐old, developed a fatal tracheotomy‐related vascular hemorrhage. The average age of patients who died with tracheotomies decreased significantly from Block 1 to Block 3; in Block 3, mean age at the time of tracheotomy was significantly lower in patients who died than in patients who survived. A comorbidity score (CS) based on the number of airway diagnoses showed that higher CSs were associated with a poorer prognosis.

Conclusions. Mortality does not seem to be strongly related to the presence of the tracheotomy tube. Overall, two diagnostic groups were found to be independently associated with a poorer prognosis, ie, mechanical ventilation and pulmonary disease. Tracheotomies performed to provide airway access during other surgical procedures were associated with a better prognosis. © 1995 Jons Wiley & Sons, Inc.
Histologic variant of the epithelial‐myoepithelial carcinoma of the salivary gland: A case report
Authors: Cheung Florence M. F. , Hioe Fei , Kong James H. B.
Published: February 2007

Background. Epithelial‐myoepithelial carcinoma (EMC) of the salivary gland is a low‐grade carcinoma. It has been widely accepted as a clinicopathologic entity only in the past decade. Histologically, the classical bimodal differentiation of inner eosinophilic ductal cells and outer layer of clear myoepithelial cells has been well documented by many authors. However, the proportion of each component may vary in different tumors or within the same tumor, and different histologic patterns have been described. The clinicopathologic findings of an epithelial‐myoepithelial carcinoma of the parotid gland in a 73‐year‐old man are presented.

Methods. Light microscopy including immunohistochemistry and ultrastructural studies were done.

Results. The various histologic patterns and bimodal differentiation of the tumor were noted.

Conclusions. The present case demonstrates the myriad of histologic patterns that can occur in epithelialmyoepithelial carcinoma. Differentiation from malignant mixed tumor is essential and possible. The importance of the awareness of its histologic variants is emphasized. © 1995 Jons Wiley & Sons, Inc.
Rehabilitation outcomes of long‐term survivors treated for head and neck cancer
Authors: de Boer Maarten F. , Pruyn Jean F. A. , van den Borne Bart , Knegt Paul P. , Ryckman Richard M. , Verwoerd Carel D. A.
Published: February 2007

Background. Little is known about the rehabilitation outcomes of long‐term survivors following treatment for head and neck cancer. There are, for example, no studies on physical and psychosocial rehabilitation outcomes of T1 glottic larynx carcinoma, despite the fact that these form the majority of head and neck cancer sites. Thus, this investigation afforded a unique opportunity for examining similarities and differences among T1 glottic larynx patients, laryngectomy patients, and those who had surgery for cancer of the oral cavity and/or oropharynx along a variety of physical and psychosocial dimensions.

Methods. To describe the impact of these three types of head and neck cancer and their treatment on the physical and psychosocial functioning of long‐term survivors, a selfreport questionnaire was completed by 110 patients treated between 2 and 6 years previously in a major cancer center.

Results. Data indicate that a higher percentage of patients treated with laryngectomy or commando procedures still experience severe psychosocial distress between 2 and 6 years after their last treatment than do patients treated with radiotherapy for a T1 carcinoma of the glottic larynx. Psychosocial and physical complaints are still reported by many laryngectomy patients, apparently the result of problems in effective communication with others. Many commando procedure patients experience problems with respect to food intake, and with disfigurement and its consequences. T1 Iarynx patients mainly experience a considerable number of physical complaints. The greater the time that had elapsed since treatment, the fewer the psychosocial problems associated with head and neck tumors. Open discussion of the illness in the family, social support, and perceptions of adequate information from the specialist are the most important predictors of positive rehabilitation outcomes.

Conclusions. This study indicates that T1 Iarynx patients report many physical complaints even though several years had elapsed since treatment. Also, Iaryngectomy patients may need psychosocial guidance for a longer posttreatment period and that health care personnel must involve the partner as much as possible in all communications. Commando procedure patients in particular feel hindered by their disfigurement and its consequences. Future research with respect to validation of the specific head and neck modules is needed.
Alterations in levels of different protein kinase C isotypes and their influence on behavior of squamous cell carcinoma of the oral cavity: εPKC, a novel prognostic factor for relapse and survival
Authors: Martínez‐Gimeno Carlos , Díaz‐Meco María T. , Domínguez Isabel , Moscat Jorge
Published: February 2007

Background. Recent results suggest that some PKC isotypes, when overexpressed, confer to cultured fibroblasts certain proliferative advantages, and enhanced tumorigenicity in nude mice, suggesting their participation in carcinogenic processes. These findings need to be validated through the investigation of potential alterations of these kinases in common forms of human cancers.

Material and Methods. In this prospective study we determined levels of different PKC isozymes by Western blot in tissue extracts from 29 human primary squamous cell carcinomas of the oral cavity, and their respective controls. These expressions were correlated with behavior of tumor and histologic characteristics.

Results. Dramatic alterations in different PKC isotypes were found. Thus, increased levels of isotypes α, β, or γ, and ε were found in most of the patients, as well as significant correlations between levels of the isotype and survival‐relapse rate and classical PKC isotypes with irregular morphology of tumoral interphase.

Conclusions. These results suggest participation of some PKC isotypes (α, β, γ, and δ) in the genesis and behavior (ε) of oral cancers. Levels of PKC could be used as prognostic marker. © 1995 Jons Wiley & Sons, Inc.
Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y‐maze task
Authors: Havekes Robbert , Timmer Marjan , Van der Zee Eddy A.
Published: February 2007

It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y‐maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus‐dependent long‐term memory is the adenosine 3′,5′ cyclic monophosphate dependent protein kinase (PKA). Here, we examined region‐specific changes in immunoreactivity (ir) of the regulatory IIα,β subunits of PKA (PKA RIIα,β‐ir) in the hippocampus during various stages of spatial learning in a Y‐maze reference task. Thereafter, we compared changes in hippocampal PKA RIIα,β‐ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RIIα,β‐ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RIIα,β‐ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RIIα,β‐ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RIIα,β protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region‐specific changes in hippocampal PKA RIIα,β‐ir and suggest a differential involvement of hippocampal subregions in match‐mismatch detection in case of Y‐maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match‐mismatch detection. © 2007 Wiley‐Liss, Inc.
CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo
Authors: Grauer Oliver M. , Nierkens Stefan , Bennink Erik , Toonen Liza W.J. , Boon Louis , Wesseling Pieter , Sutmuller Roger P.M. , Adema Gosse J.
Published: February 2007

The suppressive activity of regulatory T cells (Treg) has been implicated as an important factor limiting immune mediated destruction of tumor cells. However, not much is known about the presence and function of Treg within tumors. Here we show in a syngeneic murine glioma model a time‐dependent accumulation of CD4+FoxP3+ Treg in brain tumors. Further analysis revealed a time‐dependent upregulation of CD25, CTLA‐4, GITR and CXCR4 on intratumoral CD4+FoxP3+ Treg during tumor growth. Moreover, freshly isolated intratumoral Treg were highly suppressive when tested directly ex vivo. Treatment with anti‐CD25 monoclonal antibodies (mAbs) significantly reduced the number of these highly suppressive CD4+FoxP3+ cells within the growing tumor and provoked a CD4 and CD8 T cell dependent destruction of the glioma cells. Combining Treg depletion with administration of blocking CTLA‐4 mAbs further boosted glioma‐specific CD4+ and CD8+ effector T cells as well as antiglioma IgG2a antibody titers resulting in complete tumor eradication without any signs of autoimmunity. These data illustrate that intratumoral accumulation and activation of CD4+FoxP3+ Treg act as a dominant immune escape mechanism for gliomas and underline the importance of controlling tumor‐infiltrating Treg in glioma immunotherapy. © 2007 Wiley‐Liss, Inc.
Common variants in genes that mediate immunity and risk of multiple myeloma
Authors: Brown Elizabeth E. , Lan Qing , Zheng Tongzhang , Zhang Yawei , Wang Sophia S. , Hoar‐Zahm Shelia , Chanock Stephen J. , Rothman Nathaniel , Baris Dalsu
Published: February 2007

Multiple myeloma (MM) is a B‐cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21–84 years and 545 population‐based controls, we examined the risk of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation‐maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (−28120T, rs2107356) and FCGR2A (−120G, rs1801274) (OR = 1.91, 95% CI 1.08–3.38 and 1.95, 95% CI 1.06–3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering part of the LTA*TNF complex (LTA −82C/−90G *TNF −1036C/−487G/−417G, OR = 1.63, 95% CI 1.02–2.16) compared with the most frequently occurring haplotype observed among controls (LTA −82A/−90A *TNF −1036C/−487G/−417G). Our findings provide preliminary evidence that common genetic variants in specific immune‐mediated pathways could influence the risk of MM. © 2007 Wiley‐Liss, Inc.
Porous morphology, porosity, mechanical properties of poly(α‐hydroxy acid)–tricalcium phosphate composite scaffolds fabricated by low‐temperature deposition
Authors: Liu Li , Xiong Zhuo , Yan Yongnian , Hu Yunyu , Zhang Renji , Wang Shenguo
Published: February 2007

Tissue engineering is expected to construct complicated hominine organs composed of many different types of cells. One of the key points is the accurate controlling of scaffold material and porous morphology point by point. A new direct rapid prototyping process called low‐temperature deposition manufacturing (LDM) was proposed to fabricate scaffolds. The new process integrated extrusion/jetting and phase separation and therefore could fabricate scaffolds with hierarchical porous structures creating a wonderful environment for the growth of new tissue. The interconnected computer‐designed macropores allow cells in the new tissue to grow throughout the scaffold. Also, the parameter‐controlled micropores let nutrition in and metabolic wastes out. The macrocellular morphology, microcellular morphology, porosity, and mechanical properties of the poly(α‐hydroxy acid)‐TCP composite scaffolds prepared by the proposed method are investigated. These scaffolds with high controllability would potentially play an important role in tissue engineering. LDM could also be combined with multinozzle deposition or cell deposition to exactly control materials or cells point by point. This might bring a breakthrough to the engineered fabrication of complicated organs. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Polyelectrolyte thromboresistant affinity coatings for modification of devices contacting blood
Authors: Samoilova Nadezhda A. , Krayukhina Maria A. , Novikova Svetlana P. , Babushkina Tatyana A. , Volkov Iliya O. , Komarova Lidiya I. , Moukhametova Liliya I. , Aisina Roza B. , Obraztsova Ekaterina A. , Yaminsky Igor V. , Yamskov Igor A.
Published: February 2007

The modification of hydrophobic polyethylene/polystyrene surfaces of medical devices with bilayer/multilayer coatings (BCs/MCs) based on polyelectrolyte complexes (PEC) of modified poly(N‐vinylpyrrolidone‐co‐maleic acid) copolymer (VPMA) with chitosan, amphiphilic chitosan, or albumin was studied. The VPMA contained l‐Lysine as affinity ligand for plasminogen attached through α‐amino group. The surface properties and chemical composition of the surfaces investigated were analyzed, using sessile‐drop water contact angle measurements, attenuated total reflectance Fourier‐transform infrared spectroscopy (ATR‐FTIR), X‐ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The specific adsorption of plasminogen (precursor of fibrinolytic enzyme plasmin) from its solutions and from human blood plasma on the modified surfaces was investigated. It was established that polyelectrolyte MCs are more efficient than single‐layer BCs and the affine polymer coatings without interlayer. A thrombogenicity decrease for the materials modified with BCs and MCs was shown in in vitro and ex vivo trials. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Raman imaging for quantification of the volume fraction of biodegradable polymers in histological preparations
Authors: Nandagawali S.T. , Yerramshetty J.S. , Akkus Ozan
Published: February 2007

Postretrieval analysis of biodegradable polymeric constructs for degradation rates requires correct identification of the degradable polymer, de novo tissue and the confounding presence of a secondary polymer used for embedding. Similarities between the structures of many tissue engineering polymers may make them difficult to distinguish from the polymer used to embed explants prior to histological sectioning. In this study, we assessed the feasibility of a chemical imaging method, Raman microscopy, to discriminate between more than one polymer species. From the perspective of spectroscopy, this is not a straightforward process because of the emergence of multiple peaks, ubiquity of embedding medium, and presence of observations sourcing from points sampled at the interface of two phases. A multivariate K‐means data clustering method was used to discriminate between different polymeric components. The method was able to classify 95% of the observations to the correct category. The remaining data displayed multiple memberships because of (1) the laser spot coinciding with the interfaces of more than one phase or (2) infiltration of histological embedding polymer. Combined with multivariate analysis methods, this technique may prove useful in the future for tissue engineering and biomaterials analysis of degradation rates of, and tissue ingrowth into, polymer scaffolds. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Removal of specific antibody in vivo by whole blood immunoadsorption: Preliminary results in dogs
Authors: Bensinger W. I. , Buckner C. D. , Baker D. A. , Clift R. A. , Thomas E. D.
Published: February 2007

Effective immunoadsorption for removal of anti‐red cell antibodies from plasma using affinity columns has been demonstrated. However, the requirement of a continuous‐flow centrifuge to separate plasma increases the cost and complexity of the procedure. We have adapted red cell antigen immunoadsorption columns for use with whole blood. Effective and specific removal of anti‐red cell antibodies was achieved in actively immunized dogs.
Use of lymphoplasmapheresis or plasmapheresis in the management of acute renal allograft rejection
Authors: Kleinman Steven , Nichols Marcus , Strauss Franklin , Goldfinger Dennis
Published: February 2007

Several recent reports have documented the value of intensive plasmapheresis as an adjunct to standard immunosuppressive therapy for patients suffering acute renal allograft rejection. We have treated four rejection episodes in three patients with intensive plasmapheresis and two rejection episodes in two additional patients with intensive lymphoplasmapheresis. Five of six rejection episodes were reversed, and four of the five patients treated have retained functioning grafts for follow‐up periods ranging from 4 months to 3 years. Previous investigators have reported encouraging results using plasmapheresis, and we believe our experience supports the requirement for further controlled studies with this procedure. Moreover, we note that no previous work has been described with lymphoplasmapheresis and suggest that removal of lymphocytes, in addition to plasma, may further augment immunosuppression in the treatment of renal allograft rejection.
National center for health care technology assessment of therapeutic apheresis for rheumatoid arthritis, 1981
Authors: Heyse Stephen P. , Renault Pierre R. , Perry Seymour
Published: February 2007

The National Center for Health Care Technology coordinated the Public Health Service's assessment of therapeutic apheresis for rheumatoid arthritis in response to the Health Care Financing Administration's request for advice regarding Medicare coverage of this rapidly emerging technology. The information considered included reports available in the medical literature (as of early 1981), advice from the National Institutes of Health and Food and Drug Administration, advice from the appropriate medical societies, as well as information submitted by interested parties in response to a notice published in the Federal Register announcing the assessment. Synthesis of this information provided the basis for concluding that therapeutic apheresis for rheumatoid arthritis was considered experimental with the possible exception of treatment for life‐threatening complications such as vasculitis, cryoglobulinemia, or hyperviscosity syndrome.
The effect of plasmapheresis and drug immunosuppression on T‐cell subsets as defined by monoclonal antibodies
Authors: Kiprov Dobri D. , Dau Peter C. , Morand Paul
Published: February 2007

The number of total T‐cells and the number of helper/inducer T‐cells decreased in 27 of 31 patients with immunologic disorders treated with plasmapheresis and drug immunosuppression. The number of suppressor/cytotoxic T‐cells increased in the majority of patients. The helper/inducer to suppressor/cytotoxic cell ratio, which was initially elevated in 26 of 31 patients, decreased significantly in all but 2 patients after therapy. Ten patients were already on drug immunosuppression at the time plasmapheresis was started, and all 10 showed increased helper/inducer to suppressor/cytotoxic cell ratio despite their drug therapy. The helper/inducer to suppressor/cytotoxic cell ratio decreased in all ten patients after plasma exchange. The number and the percentage of total T‐cells and helper/inducer cells decreased from prepheresis levels while the number and the percentage of suppressor/cytotoxic cells increased. Plasmapheresis, in combination with drug immunosuppression, was effective in decreasing the elevated helper/inducer to suppressor/cytotoxic cell ratio in disorders of the immune system. In contrast, patients on immunosuppressive drug therapy alone had persistently high immunoregulatory ratio.
Selective removal of sickle cells with the IBM 2997 continuous flow blood cell separator
Authors: Lenes B. , Klein H. G. , Lakatos E.
Published: February 2007

Partial red cell exchange transfusion is used to manage several complications of sickle cell anemia. Reports have stressed the safety, case, and speed of red cell exchange procedures performed with blood cell separators, but little information exists concerning operating conditions for the most efficient removal of hemoglobin S (HbS) containing cells. We performed 13 red blood cell exchange transfusions with the IBM 2997 continuous flow blood cell separator on two previously transfused adult homozygous (SS) sickle cell patients. We used both a single stage and a dual stage disposable pathway and varied rotor speed, collection port, and collection interface independently. The patients' baseline percentage HbS ranged from 28 to 64% (mean = 46%); post exchange values ranged from 19.1 to 46% (mean = 32%). Thirty‐three of 34 specimens collected from the white cell or platelet port showed a higher percentage of HbS in the collection line compared to simultaneous patient samples. Mean enrichment was 9.4% (range = −4.0 to 35.5%). There was an inverse relationship between the hemoglobin concentration and the percentage of HbS in the collected specimens (p = 0.001; N = 45). Differential separation of sickle cells should decrease the volume of blood required for partial red cell exchange of selected SS patients.
Subclavian vein catheterization for apheresis access
Authors: Spindler Joseph S.
Published: February 2007

We have inserted Shiley Vas‐Caths® into the subclavian veins of 20 patients. These indwelling catheters are used for apheresis and some were maintained up to 3 months. Of the 430 apheresis procedures performed, 30 (6.9%) had good peripheral vein access while 400 (93.1%) required subclavian vein catheterization. No complications, including infection and blood clotting, have been recorded. The only contamination noted was normal skin flora cultured on the outside of the exposed portion of the cannula. We attribute our success to limited catheter manipulation, frequent dressing changes, and adhering to strict, sterile procedures.
Plasma exchange: A controlled study of the effect in patients with Raynaud's phenomenon and scleroderma
Authors: McCune Mark A. , Winkelmann R. K. , Osmundson Philip J. , Pineda Alvaro A.
Published: February 2007

Six female patients with stage I and II vascular scleroderma and Raynaud's phenomenon were treated with plasma exchange and placebo plasma exchange. Placebo exchange consisted of the return of the patient's own separated plasma. No consistent long‐term objective improvement was demonstrated in patients treated with either plasma exchange or placebo plasma exchange. Immediate increases in pulse volume, digital blood pressure, and skin temperature occurred in some patients with both procedures. Mechanisms of change remain unexplained, and further study is warranted.
Plasma exchange in autoimmune hemolytic anemia (AIHA)
Authors: Silberstein L. E. , Berkman E. M.
Published: February 2007

Plasma exchange therapy in autoimmune hemolytic anemia (AIHA) was used in four patients (two with warm hemolytic anemia and two with cold hemolytic anemia). The size of each plasma exchange approximated 1 plasma volume; three consecutive daily exchanges removed 80–90% of the immunoglobulins—immunoglobulin G (IgG) and immunoglobulin M (IgM)—. complement (C3, C4), and reduced antibody titers. Transfusion requirements dramatically decreased after plasma exchange in each case. In two patients, red blood cell (RBC) survival studies were performed to more accurately assess the effect of plasma exchange therapy, since steroid and/or immunosuppressive therapy was given concomitantly. In one case of cold AIHA, homologous 51Cr‐RBC were injected 4 days prior to plasma exchange and repeat injection (same donor) following completion of plasma exchange. The survival curve prior to plasma exchange therapy had a T 1/2 = 7.8 days (r = −0.988) and after plasma exchange therapy had a T 1/2 = 20.4 days (r = −0.925). RBC survival studies using homologous 51Cr‐RBC were also performed in a patient with warm AIHA. The survival curve before plasma exchange had a T 1/2 = 2 days (r = −0.95), and postplasma exchange a T 1/2 = 1.8 days (r = −0.91). Plasma exchange therapy seems to have a beneficial effect in cold rather than warm autoimmune hemolytic anemia.