Comparative study of new autologous material, bone-cartilage composite graft, for ossiculoplasty with Polycel® and Titanium.

OBJECTIVE: Ossiculoplasty is a surgical procedure that recreates sound transmission of the middle ear in conductive hearing loss. Various materials have been used for ossicular reconstruction, but the most ideal material for ossiculoplasty remains controversial. The purpose of this study was to introduce a novel method of autologous ossiculoplasty, bone-cartilage composite graft (BCCG) and to compare its surgical results with different types of ossiculoplastic prostheses. STUDY DESIGN: A retrospective study was performed in a tertiary referral centre. METHODS: Data of 275 patients who received ossiculoplasty using the three different materials of BCCG, Polycel® and titanium were analysed according to type of ossiculoplasty: partial or total ossicular replacement prosthesis (PORP or TORP). Hearing results, complication rates and clinical parameters including age, sex, past history, preoperative diagnosis and surgery type were compared among different groups. RESULTS: Ossiculoplasty with BCCG showed satisfactory hearing outcomes and the lowest complication rate among the three different materials. In particular, its extrusion rate was 0%. CONCLUSION: We propose that the BCCG technique is a useful alternative method for ossiculoplasty, with proper patient selection.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

Agreement rates among single photon emission computed tomography using gallium-67, computed axial tomography and lymphangiography for Hodgkin disease and correlation of image findings with clinical outcome.

BACKGROUND: This study was undertaken to systematically evaluate the agreement rates among single photon emission computed tomography using gallium-67 (Ga-67 SPECT), lymphangiography (LAG), and computed axial tomography (CT) scan findings for Hodgkin disease and to correlate radiologic findings with clinical outcome. METHODS: One hundred three previously untreated patients with Hodgkin disease who had Ga-67 SPECT scan between August 1992 and December 1994 at our institution form the basis of this study. The agreement rates among Ga-67 SPECT, LAG, and CT scan findings were calculated by sites from the pretreatment evaluation throughout the courses of chemotherapy. The probabilities of recurrence or progression by sites were correlated with the radiologic findings. RESULTS: The median follow-up was 3 years. The pretreatment agreement ranged from 75% to 100% between Ga-67 SPECT and CT scans, 85-100% between CT scan and LAG, and 74-99% between Ga-67 SPECT and LAG. A greater variation in agreement was observed once chemotherapy was started, the site with the least agreement being the mediastinum. The most common site of the recurrence or progression was also the mediastinum. When the CT scan showed persistent abnormality even after Ga-67 SPECT turned negative after chemotherapy, the chances of mediastinal recurrence or progression were 3 in 34 and 3 in 18 after 1-3 cycles and 4-6 cycles, respectively. CONCLUSIONS: Although there was a relatively high correlation between Ga-67 SPECT and the other modalities, the intrinsic limitation of planar Ga-67 was still observed in Ga-67 SPECT especially in the mediastinum. There was still a moderate risk of mediastinal recurrence or progression even after residual CT scan abnormality lost gallium avidity from chemotherapy.

L-arginine infusion dilates coronary vasculature in patients undergoing coronary bypass surgery.

BACKGROUND: Nitric oxide-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-arginine, a precursor for nitric oxide production, dilate the coronary vascular bed of patients undergoing coronary artery bypass graft surgery. METHODS: Twenty patients scheduled for coronary artery bypass graft surgery surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow was measured with a transit time flow probe, and coronary vascular resistance was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride [30 g]) over 15 min. Arterial blood samples for the determination of L-arginine and L-citrulline levels were drawn before, 10 min after starting infusion, and 10 min after end of infusion. RESULTS: The placebo group experienced an increase in mean arterial pressure and coronary vascular resistance and a decrease in graft blood flow. Patients in the L-arginine group maintained their baseline values. Mean arterial pressure (L-arginine, 88+/-17 to 92+/-13 mmHg vs. placebo, 80+/-12 to 92+/-9 mmHg, P = 0.021), coronary vascular resistance (L-arginine, 97,000+/-60,000 to 99,600+/-51,000 dynes x s x cm(-5) vs. placebo, 81,000+/-69,000 to 117,000+/-64,000 dynes x s x cm(-5), P = 0.05), and graft blood flow (L-arginine, 55+/-25 to 50+/-19 ml/min vs. placebo, 60+/-34 to 46+/-18, P = 0.05) remained more stable in the L-arginine-treated patients. CONCLUSIONS: Systemic L-arginine infusion reduced postbypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.

Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication.

Human rhinovirus, the chief cause of the common cold, contains a positive-sense strand of RNA which is translated into a large polyprotein in infected cells. Cleavage of the latter to produce the mature viral proteins required for replication is catalyzed in large part by a virally encoded cysteine proteinase (3Cpro) which is highly selective for -Q approximately GP- cleavage sites. We synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone esters (e.g., Boc-Val-Leu-Phe-vGln-OR: R = Me, 1; R = Et, 2) and evaluated them as inhibitors of HRV-14 3C protease (3Cpro). Compounds 1 and 2 and several related tetra- and pentapeptide analogues rapidly inactivated 3Cpro with submicromolar IC50 values. Electrospray mass spectrometry confirmed the expected 1:1 stoichiometry of 3Cpro inactivation by 1, 2, and several other analogues. Compound 2 also proved to be useful for active site titration of 3Cpro, which has not been possible heretofore because of the lack of a suitable reagent. In contrast to 1, 2, and congeners, peptidyl Michael acceptors lacking a P4 residue have greatly reduced or negligible activity against 3Cpro, consistent with previously established structure-activity relationships for 3Cpro substrates. Hydrolysis of the P1 vinylogous glutamine ester to a carboxylic acid also decreased inhibitory activity considerably, consistent with the decreased reactivity of acrylic acids vs acrylic esters as Michael acceptors. Incorporating a vinylogous methionine sulfone ester in place of the corresponding glutamine derivative in 1 also reduced activity substantially. Compounds 1 and 2 and several of their analogues inhibited HRV replication in cell culture by 50% at low micromolar concentrations while showing little or no evidence of cytotoxicity at 10-fold higher concentrations. Peptidyl Michael acceptors and their analogues may prove useful as therapeutic agents for pathologies involving cysteine proteinase enzymes.

Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity.

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

Thyroid lymphomas stages IE and IIE: comparative results for radiotherapy only, combination chemotherapy only, and multimodality treatment.

This study was undertaken to ascertain the influence of both more precise staging and more intensive treatment on results in 38 patients with Stage IE and IIE lymphomas of the thyroid. These patients were admitted between 1947 and 1984. Using the modified Rappaport system, the disease was classified as diffuse large cell in 32 patients. The initial investigation included lymphangiography in 25 patients, five of which had a staging laparotomy. The assigned stages were IEA--11, IEB--1, and IIEA--26. Treatment consisted of definitive radiotherapy alone in 15; combination chemotherapy and radiotherapy in 14; and chemotherapy alone in 6 patients. The remaining three patients were treated with surgery alone. In general, combination chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, and prednisone, with or without bleomycin (CHOP +/- Bleo). The overall 5-year survival and disease-free survival were 72 and 64%, respectively. For patients treated with radiotherapy only, results depended on stage. For Stage IE, the survival and disease-free survival were 100 and 83%, respectively. The corresponding Stage IIE results were 88 and 75%. Within this group, results were better for a subset of patients where disease did not involve the mediastinum. Survival and disease-free survival for combined modality treatment were both 77% (10 of these 17 patients had Stage IIE disease). Survival and disease-free survival for combination chemotherapy were 53 and 30% (all had Stage IIE disease). In conclusion, radiotherapy alone is excellent treatment for disease limited to the thyroid with or without cervical adenopathy. Results for patients with mediastinal extensions was unsatisfactory and the addition of combination chemotherapy is indicated.

A comparative analysis of lymphomas involving Waldeyer's ring and the nasal cavity and paranasal sinuses.

The two major extranodal sites for malignant lymphoma of the head and neck are Waldeyer's ring and the nasal cavity and paranasal sinuses. The clinical manifestations, treatment, and survival results are presented for 137 patients with primary lymphoma of Waldeyer's ring and 38 patients with primary lymphoma of the nasal cavity and paranasal sinuses. The similarities of and differences between the two sites are discussed and compared to their more common counterparts the carcinomas. The results of this study indicate that the TNMAJCC method of staging Ann Arbor stage IE and IIE non-Hodgkin's lymphoma is a reliable prognostic indicator for these sites and should be considered when determining treatment.

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck.

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.