Ki-67 immunostaining and prognosis in laryngeal cancer

A 7-year-old male Husky dog developed atrophy of the right masseter muscle and pruritus of the right side of the face. A myogenic origin was excluded using muscular biopsy. Electrophysiologically, there was involvement of the motor and sensory fibers of the trigeminal nerve, suggesting a lesion located between the brainstem and the trigeminal ganglion. On MRI examination, a nodular mass was detected in the right caudal fossa. This mass was characterized by intense enhancement after injection of contrast medium. Because of the progressive clinical signs, electrophysiology, and MRI results, a presumptive diagnosis of a trigeminal nerve schwannoma was made. The animal's condition improved slightly with corticosteroids. The dog underwent euthanasia 3 months after initial presentation. Necropsy was not performed.     

The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives

The multidrug resistant (MDR) phenotype has been suspected as a major cause of treatment failure in hematologic malignancies. Numerous studies have investigated the expression of the MDR1 gene product, P-glycoprotein, in leukemia, lymphoma and myeloma. Studies in myelogenous leukemia and myeloma have so far provided best evidence for a significant correlation between P-glycoprotein expression and response to chemotherapy, although large discrepancies in the proportion of positive cells limit any definite conclusion. Differences in P-glycoprotein detection techniques and methodology may account for the divergent results thus emphasizing the necessity for standardized methods of detection. Despite this, encouraging clinical results have been obtained using MDR modulators in combination with conventional chemotherapy to inhibit the activity of the P-glycoprotein pump. The paper summarizes currently available clinical data and provides guidelines for future trials aimed to reverse the MDR phenotype. The potential of idarubicin to overcome the MDR phenotype is also discussed.     

Functional voice quality assessment in curative microsurgery of laryngeal malignancies. Postoperative voice rehabilitation based on the "laryngeal double valve function"

According to Negus and Pressman the sphincter systems of the vocal folds and the ventricular folds form a respiratory "laryngeal double valve function". Correspondingly, we found a physiological phonation system of the glottis and a pathological-compensatory one of the supraglottis. They appear to be regulated through an automatic phonatory control system with the glottal phonatory function evidently acting as sensor level. In order to confirm this hypothesis, objective voice analyses with glottal-relevant parameters of 26 voice-rehabilitated patients after minimally invasive laser surgery of glottal carcinomas are presented and integrated into a "hoarseness diagram" with the coordinates roughness and breathiness. Using statistically deliminated acoustic dusters, our data show a qualitative hierarchy of different postoperative phonation mechanisms. They demonstrate the influence of the vibratory capacity of glottal and supraglottal structures on the quality of the vibratory closure. Both functional parameters evidently determine the resulting voice quality in the sense of our hypothesis.     

Future treatment options for haematological malignancies

This paper is the last in a series looking at haematological malignancies. It pinpoints where we are now in the treatment of leukaemias before discussing current and future developments.     

Radiotherapy in the treatment of dermatologic malignancies

A large set of monoclonal antibodies (MAbs) directed against the fusion glycoprotein complex F1F2 of bovine respiratory syncytial virus (BRSV) and several polyclonal sera from infected or vaccinated animals were tested in Pepscan to locate linear epitopes on the F-protein. The polyclonal sera mapped to antigenic sites that correspond exactly to known antigenic sites on the F protein of human RSV. Only the neutralizing MAb 3 could be mapped with Pepscan. MAb 3 reacted with three successive overlapping linear peptides that shared the amino acid sequence 173STNKAVVSLS182. The sequence of this novel neutralization site is conserved in all known BRSV- and human RSV-strains and is located on the N-terminus of F1, adjacent to the hydrophobic, putative fusion-related region. This region is probably part of a central coiled-coil stem that is structurally conserved in paramyxovirus fusion and orthomyxovirus hemagglutinin glycoproteins. This linear conserved epitope may be a potential candidate for a peptide-based vaccine which can induce neutralizing antibodies against all groups and subgroups of RSV. Furthermore, the proposed structural features of the neutralization site may aid in the design of a peptide-based vaccine.     

复发性脑出血的治疗与预后分析

目的:通过对复发性脑出血患者的治疗和影响预后的因素进行分析,探讨复发性脑出血的预防与治疗措施.方法:比较存活患者与死亡患者情况,将存活的24例与死亡的8例患者的一般资料(年龄、性别)、临床资料(血压、血脂、出血部位、出血量等)和治疗等情况进行比较.并在治疗后随访存活患者1年后预后情况.结果:32例复发性脑出血患者治疗结果,治愈18例,好转6例,死亡8例,有效率占75%.住院时间为7～68d,平均19.5d.死亡患者死亡年龄平均为65.1±1.2岁;存活患者年龄平均为43.1±1.4岁,二者进行比较,P＜0.05,差异具有统计学意义,且存活例复发性脑出血患者治疗结果患者年龄小于死亡患者.性别两组无差异(P＞0.05).存活患者与死亡患者血压、血脂、出血部位、出血量和治疗等情况比较,P均＜0.05,差异有统计学意义.存活患者出血位置以基底节最多,死亡患者以脑干出血为主.24例存活患者中仅有1例出血次数≥3次,死亡患者7例均为出血次数≥3次.1年后随访,存活患者中1例患者死亡,1例出现出血复发.     

Monoclonal antibodies in the treatment of human B-cell malignancies

Monoclonal antibody technology emerged in the 1970's and was greeted by a wave of optimism. Many believed this new form of therapy would be effective in the treatment of human cancers. Early clinical trials in B-cell lymphomas demonstrated both the potential and limitations of unlabeled murine monoclonal antibody therapy, and taught us valuable lessons regarding the importance of the antibody structure, and nature of the targeted antigen. Since that time modifications in antibody structure and careful selection of target antigen have improved the clinical efficacy of these agents. Clinical trials using humanized antibodies have demonstrated that human/mouse chimeric antibodies and humanized antibodies have enhanced anti-tumor activity, decreased immunogenicity, and a very favorable toxicity profile. Radiolabeled monoclonal antibodies can induce durable remissions in lymphoma with toxicity limited largely to bone marrow suppression. Clinical trials with immunotoxins have demonstrated anti-tumor activity but also have been associated with significant toxicity. Standard treatment options for B-cell lymphoma will soon include antibody-based therapies. Further basic and clinical research is needed so we can understand more thoroughly the mechanisms responsible for the observed anti-tumor effects, and explore more extensively the best approach to their clinical use.     

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: a review

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, represent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Intergroup Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas.     

Cancers of the papilla of vater: mutator phenotype is associated with good prognosis

Cancer of the papilla (ampulla) of Vater is an uncommon disease that kills 60% of affected patients. There is general agreement that local spread of the tumor (T stage) is the only significant and independent prognostic factor for this cancer, whereas the predictive value of tumor grade and lymph node metastases is controversial. The genetic anomalies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurrence of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (RER-positive) cancers. Ten microsatellites from five different chromosomes were amplified by PCR from both normal and cancer tissue DNA of the same patients. A tumor was defined as RER-positive when microsatellite instability was found in the majority (>/=6) of the loci analyzed. Five cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas RER-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (12%) patients belonged to cancer-prone families and four (16%) were cancer-prone individuals.     

Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.     

Pilot trial of ribavirin for the treatment of laryngeal papillomatosis

The antiviral drug ribavirin was used as an adjunct to laser surgery for the treatment of patients with laryngeal papillomatosis (LP). An uncontrolled clinical trial for four patients with ribavirin treatment at a daily dose of 23 mg/kg was performed. Three adults received drug prior to laser surgery and continuing orally for 6 months. One infant was treated for 3 months. Two adults achieved complete remissions for at least 2 consecutive months, and both patients developed only minimal recurrent disease in 4 months of follow-up. The other adult and the child sustained a partial response and an increased interval between the required surgeries. Ribavirin caused only a mild, reversible reduction in hemoglobin and reticulocytosis. This preliminary trial shows that ribavirin may be an effective therapy in combination with surgery for LP in a larger controlled clinical trial.     

Preliminary study of two methods of treatment for laryngeal nodules

To date, a limited number of formal studies have assessed the efficacy of voice therapy for laryngeal nodules. The present study represents a preliminary stage of inquiry in a series of planned studies on this topic. Thirteen women with nodules participated as paid subjects. Some subjects received "confidential voice therapy," some received "resonant voice therapy," and some received no therapy (control condition) over a period of approximately 2 weeks. Pre- and post-therapy measures of phonatory effort, auditory-perceptual status of voice, and laryngeal appearance provided evidence of a benefit from therapy. Baseline measures were then repeated 2 weeks after therapy was terminated. The final results indicated that, for auditory-perceptual and phonatory effort measures, the likelihood of benefiting from therapy directly covaried with compliance scores (reflecting the reported extraclinical utilization of the therapy technique), but not with therapy type (confidential vs. resonant voice therapy). At this level, the results point to the importance of assessing not only therapy type but also compliance in future, larger studies. A series of other positive and negative factors in the present research design were identified based on the results. These should be considered in future studies.     

Mannhein index in the prognosis and treatment of acute peritonitis

Coronary Artery Disease (CAD) remains the major cause of mortality and morbidity in the Western World. The oxidation of low-density lipoproteins (LDLs) by free radicals is associated with initiation of atherosclerosis and therefore, development of CAD. LDLs are protected from oxidation by antioxidants and in times of antioxidant deficiency are more likely to be oxidized. Hypercholesterolaemic patients are at a higher cardiovascular risk and may, therefore, require more antioxidant protection. Increased consumption of red wine containing antioxidants is thought to account for the lower incidence of CAD in Mediterranean countries. Red wine, although rich in antioxidants, is not suitable as routine therapy for prevention of CAD. OBJECTIVE: To evaluate the effects of a capsule formulation of an antioxidant polyphenolic extract of grapes on serum total antioxidant activity and vitamin C and E levels. METHOD: A single-blinded randomised, placebo-controlled cross-over study was undertaken in 20 young volunteers. Subjects were given two capsules containing 300 mg of grape procyanidin extracts (Leucoselect-phytosome) or placebo daily for 5 days. Blood samples were taken at the start of the study and end of the study and assayed for antioxidant activity and vitamins C and E levels. After a washout period of at least 2 weeks, the study was repeated with the second treatment. RESULTS: The extract had no effect on serum vitamins C and E levels but increased serum total antioxidant activity (TAC). On day 5, TAC increased from 408.1+/-22.9 to 453.3+/-453.3 micromol/l trolox equivalents 1 hour postdose. CONCLUSION: The capsules increased serum antioxidant activity but the longer-term clinical implications need to be assessed in further randomised clinical trials.     

Diagnosis, prognosis, and standard treatment of multiple myeloma

The diagnosis of multiple myeloma (MM) is often difficult; most patients present with asymptomatic gammopathy. The only findings that confirm a diagnosis of MM are an elevation in the M-component or extension of the lytic bone lesions that are the hallmark of the disease. Tests that delineate plasma cell biology, such as plasma cell proliferation rate, are helpful; magnetic resonance imaging can disclose bone marrow lesions leading to subsequent osteolytic disease. After the diagnosis of MM has been established and prognostic factors identified, the appropriate therapy can be determined. Melphalan and prednisone are no longer considered to be the "gold standard" of therapy. In fact, this approach is suitable for less than half of patients with myeloma. This article presents guidelines for standard treatment options and examines the efficacy of new high-dose chemotherapy approaches.